MedWorm: Alport Syndrome

Renal diseases associated with hematuria in children and adolescents: a brief tutorial.

Ultrastructural Pathology — Wed, 08 Feb 2012 03:06:09 +0100

Authors: Hicks J, Mierau G, Wartchow E, Eldin K Abstract The detection of microscopic hematuria in a child's urine prompts evaluation for renal and urinary bladder causes. Microscopic hematuria identified during a routine physical examination by the pediatrician is much more common than macroscopic hematuria. Persistent microscopic hematuria is particularly worrisome and may require a percutaneous needle core kidney biopsy to determine whether the etiology is secondary to glomerular disease, tubulointerstitial disease, urinary tract infection, urinary tract structural abnormalities, medications, or toxins. This paper reviews the epidemiology, pathologic features, pathogenesis, treatment, and outcome of familial hematuria (Alport syndrome [hereditary nephritis]), thin basement membr...

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Fibromuscular dysplasia: a differential diagnosis of vasculitis

Revista Brasileira de Reumatologia — Fri, 03 Feb 2012 10:19:07 +0100

A displasia fibromuscular (DFM) envolve artérias de pequeno e médio calibre e é uma causa bem conhecida de hipertensão em mulheres jovens caucasianas, quando envolve as artérias renais. A etiologia da DFM permanece desconhecida, a despeito de inúmeras teorias. Há suspeita de um componente genético, já que a doença atinge primariamente caucasianos. Também é descrita associação entre DFM e antígeno de histocompatibilidade HlA-DRw6. Os principais sítios acometidos são as artérias renais, cerebrais, carótidas, viscerais, ilíacas, subclávias, braquiais e poplíteas. As manifestações clínicas correlacionam-se com o sítio acometido, e a hipertensão arterial sistêmica é um sintoma frequente pelo acometimento das artérias renais em 60%-75% dos casos. O diagnóstico da D...

Good obstetric outcome of consecutive pregnancies in a woman with Alport syndrome

Archives of Gynecology and Obstetrics — Fri, 20 Jan 2012 07:05:22 +0100

Content Type Journal ArticleCategory Letter To the EditorPages 1-2DOI 10.1007/s00404-012-2225-6Authors Shigeki Matsubara, Department of Obstetrics and Gynecology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, JapanShigeaki Muto, Department of Nephrology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan Journal Archives of Gynecology and ObstetricsOnline ISSN 1432-0711Print ISSN 0932-0067 (Source: Archives of Gynecology and Obstetrics)

Attitudes toward genetic diagnosis and prenatal diagnosis of X‐linked Alport syndrome in China

Nephrology — Thu, 12 Jan 2012 05:00:00 +0100

Conclusion: Most of Chinese XLAS families show positive attitudes and desire the new discovery in the treatment and diagnosis, about 80% of respondents would approve for prenatal testing with a desire for selective abortion rather than prediction the health of a future child. (Source: Nephrology)

Etiology of chronic renal failure in Jenin district, Palestine.

Saudi Journal of Kidney Diseases and Transplantation — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Abumwais JQ Abstract A study was conducted on chronic renal failure patients treated by medications or by hemodialysis at The Martyr Dr. Khalil Sulaiman Hospital in Jenin city, Palestine, from 1/8/2005 to1/8/2006 to know the underlying etiology of chronic renal failure. The subjects included were 84 patients. The information was obtained from files of the patients. The diagnosis was based on medical history, laboratory tests, X-rays, CT scans, ultrasound and renal biopsies. The results showed that the three most common causes of chronic renal failure in Jenin district were diabetes mellitus (33.32%), hypertension (16.7%), and chronic glomerulonephritis (13.1%). Inherited kidney diseases formed an important percentage (17.85%) and included primary hyperoxaluria (10.71%), Al...

Outcome of Renal Transplantation in Alport's Syndrome: A Single-Center Experience

Transplantation Proceedings — Sun, 01 Jan 2012 05:00:00 +0100

Conclusion: Graft and patient survivals were acceptable among transplant recipients with AS despite the risk of anti-GBM nephritis. (Source: Transplantation Proceedings)

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Clinical utility gene card for: Alport syndrome

European Journal of Human Genetics — Wed, 14 Dec 2011 05:00:00 +0100

Authors: Jens Michael Hertz, Mads Thomassen, Helen Storey & Frances Flinter (Source: European Journal of Human Genetics)

Book: Kidney Steps

Sound Medicine — Sun, 11 Dec 2011 05:00:00 +0100

And finally this week: a mother and daughter share what they've learned -- the hard way -- about kidney disease. When Victoria Hulet needed a kidney transplant due to a hereditary disorder called Alport's Disease, her daughter Jennifer volunteered to be a donor. As the two became immersed in the transplant process, they discovered there was very little patient friendly material available. .... (Source: Sound Medicine)

Late Presentation of Alport Posttransplantation Anti-Glomerular Basement Membrane Disease

Transplantation Proceedings — Thu, 01 Dec 2011 05:00:00 +0100

We describe a female patient with Alport disease who developed antiglomerular basement membrane nephritis late after kidney transplantation during the treatment of an acute bacterial pyelonephritis and discuss the potential role of the infection as a trigger for the development of this nephritis. (Source: Transplantation Proceedings)

Twenty-one novel mutations identified in the COL4A5 gene in Chinese patients with X-linked Alport's syndrome confirmed by skin biopsy

Nephrology Dialysis Transplantation — Fri, 25 Nov 2011 05:00:00 +0100

Conclusions. We have identified 25 pathogenic mutations in 35 Chinese families with XLAS. Skin biopsy is effective for the diagnosis of XLAS. (Source: Nephrology Dialysis Transplantation)

Low birth weight and nephron mass and their role in the progression of chronic kidney disease: a case report on identical twins with Alport disease

Nephrology Dialysis Transplantation — Fri, 25 Nov 2011 05:00:00 +0100

We report the outcomes of 47-year-old monozygotic twins with Alport syndrome, who share the same maternal and genetic factors; however, in adulthood have discordant trajectories in the decline of their renal function. The twin with the more rapid progression to renal failure was born with low birth weight (LBW), suggesting congenital nephron deficiency and increased susceptibility to progressive renal disease, despite having the same genetically inherited kidney condition. This ‘natural experiment’ adds further credence to the hypothesis that LBW contributes to the susceptibility to chronic kidney disease. We suggest further studies and surveillance for this high-risk group of infants in order to gain additional insights into the impact of perinatal factors such as LBW. (Source...

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Behavioral and Ecological Consequences of Sex-Based Differences in Gustatory Anatomy in Cebus apella.

Anatomical Record — Tue, 01 Nov 2011 04:00:00 +0100

This study examines sex differences in FPs and TPs (a TB surrogate) in 11 Cebus apella to test the hypothesis that higher FP density in females may be an adaptation specific to reproductive strategies of females. Tongues were imaged using an environmental scanning electron microscope; from these images FP surface area, FP density, TP count, and TP densities were calculated. We found that there were no significant differences between males and females in the number of TPs per FP. However, we did find that females do have larger FP surface areas and higher FP densities than males. The anatomical evidence indicates that females may have greater taste sensitivity than males because females have more FP than males. Future research on food preference and selection in Cebus is expected to show se...

Presentation of seven members of a family with the Alport's syndrome.

Saudi Journal of Kidney Diseases and Transplantation — Tue, 01 Nov 2011 04:00:00 +0100

Authors: Elezi Y, Rugova B, Hasani A, Elezi E, Zylfiu B, Telaku S, Rrudhani I PMID: 22089792 [PubMed - in process] (Source: Saudi Journal of Kidney Diseases and Transplantation)

Clear lens extraction in Alport syndrome with combined anterior and posterior lenticonus or ruptured anterior lens capsule

Journal of Cataract and Refractive Surgery — Sun, 23 Oct 2011 05:15:52 +0100

We describe the results of clear lens extraction in 7 eyes of 4 Alport-syndrome patients. Three patients (6 eyes) had both anterior and posterior lenticonus; the fourth patient had spontaneous rupture of the anterior lens capsule, resulting in an acute drop in vision. Clear lens extraction was an effective method for visual rehabilitation in Alport syndrome patients.Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. (Source: Journal of Cataract and Refractive Surgery)

Synchronous bilateral urothelial cancer in a kidney recipient

International Journal of Urology — Mon, 17 Oct 2011 04:00:00 +0100

We report a 25‐year‐old male kidney recipient with Alport syndrome who developed bilateral synchronous urothelial cancer after transplantation. At the age of 16 this patient was referred to our clinic for a kidney transplantation. A living related donor kidney transplantation was performed with cyclosporin‐based quadruple immunosuppression. He experienced no acute rejection and his graft function was excellent after transplantation. Nine years after transplantation, he complained of asymptomatic gross hematuria and was diagnosed as having a bilateral urothelial cancer in the native upper urinary tracts. A bilateral total nephroureterectomy was undertaken, and the postoperative pathological diagnosis was advanced bilateral urothelial carcinoma. The patient received adjuvant gemcitabin...

Advances in Alport syndrome diagnosis using next-generation sequencing

European Journal of Human Genetics — Wed, 07 Sep 2011 04:00:00 +0100

Authors: Rosangela Artuso, Chiara Fallerini, Laura Dosa, Francesca Scionti, Maurizio Clementi, Guido Garosi, Laura Massella, Maria Carmela Epistolato, Roberta Mancini, Francesca Mari, Ilaria Longo, Francesca Ariani, Alessandra Renieri & Mirella Bruttini (Source: European Journal of Human Genetics)

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Genetics and CKD

Advances in Chronic Kidney Disease — Thu, 01 Sep 2011 04:00:00 +0100

The diagnosis of hereditary monogenic kidney diseases is frequently delayed, in part because of physicians’ unfamiliarity with the relatively rare conditions or because of the late onset of symptoms in some patients. Molecular biology methods have clarified the underlying mutations in several types of CKD, and in the process have revealed previously unknown genes and pathogenetic pathways. Mutations affecting the integrity of the glomerular filtration barrier cause proteinuria or nephrotic syndrome; different types of Alport syndrome are caused by mutations in glomerular basement membrane type IV collagen; dysfunction of the primary cilium of tubule cells may lead to a variety of inherited progressive tubulointerstitial diseases; atypical hemolytic-uremic syndrome is frequently caused by...

Age and gender may affect posterior reversible encephalopathy syndrome in renal disease

Pediatric Nephrology — Sun, 07 Aug 2011 05:52:05 +0100

Abstract It remains elusive what factors affect posterior reversible encephalopathy syndrome (PRES). Eleven PRES children, all with acute glomerulonephritis, Alport syndrome, and lupus nephritis, 5 with nephrosis, and 3 renal transplant recipients, were studied. PRES recurred in 1 patient. Neurological symptoms were graded as 1: mild (headache, nausea/vomiting, or tremor), 2: moderate (vision change), and 3: severe (mental dysfunction, cerebellar symptoms, seizures, recurrence of seizures, and coma). Magnetic resonance imaging was graded as 1: subtle change, 2: abnormal large areas, and 3: complete involvement of the regions. The common symptoms were seizures (100%), headache (82%), nausea/vomiting (73%), coma (55%), and vision change (46%). Seizures recurred in 7 (64%). A...

Tumor necrosis factor‐α‐drives Alport glomerulosclerosis in mice by promoting podocyte apoptosis

The Journal of Pathology — Thu, 04 Aug 2011 03:23:30 +0100

AbstractChronic renal failure involves the progressive loss of renal parenchymal cells. For example, Alport syndrome develops from mutated type IV collagen that fosters the digestion of glomerular basement membranes and podocyte loss, followed by progressive glomerulosclerosis, i.e. Alport nephropathy. Here we show that autosomal recessive Alport nephropathy in collagen4a3‐deficient mice is associated with an increased intrarenal expression of the proapoptotic cytokine tumor necrosis factor‐alpha (TNF‐α), in glomerular cells including podocytes as well as in infiltrating leukocytes. We therefore hypothesized that TNF‐α contributes to Alport glomerulosclerosis by inducing podocyte apoptosis. To address this issue we treated 4‐week old collagen4a3‐deficient mice with either veh...

Tumour necrosis factor‐α drives Alport glomerulosclerosis in mice by promoting podocyte apoptosis

The Journal of Pathology — Wed, 03 Aug 2011 04:00:00 +0100

AbstractChronic renal failure involves the progressive loss of renal parenchymal cells. For example, Alport syndrome develops from mutated type IV collagen that fosters the digestion of glomerular basement membranes and podocyte loss, followed by progressive glomerulosclerosis, ie Alport nephropathy. Here we show that autosomal recessive Alport nephropathy in collagen 4a3‐deficient mice is associated with increased intrarenal expression of the pro‐apoptotic cytokine tumour necrosis factor‐alpha (TNF‐α) in glomerular cells including podocytes as well as in infiltrating leukocytes. We therefore hypothesized that TNF‐α contributes to Alport glomerulosclerosis by inducing podocyte apoptosis. To address this issue, we treated 4‐week‐old collagen 4a3‐deficient mice with either ...

Efficacy and safety of losartan in children with Alport syndrome--results from a subgroup analysis of a prospective, randomized, placebo- or amlodipine-controlled trial

Nephrology Dialysis Transplantation — Wed, 27 Jul 2011 23:00:00 +0100

Conclusions. Losartan significantly lowered proteinuria and was well tolerated after 12 weeks of treatment in children aged 1–17 years with proteinuria secondary to Alport syndrome with or without hypertension, a population that has not previously been rigorously studied. (Source: Nephrology Dialysis Transplantation)

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The role of molecular genetics in diagnosing familial hematuria(s)

Pediatric Nephrology — Tue, 21 Jun 2011 17:59:10 +0100

Abstract Familial microscopic hematuria (MH) of glomerular origin represents a heterogeneous group of monogenic conditions involving several genes, some of which remain unknown. Recent advances have increased our understanding and our ability to use molecular genetics for diagnosing such patients, enabling us to study their clinical characteristics over time. Three collagen IV genes, COL4A3, COL4A4, and COL4A5 explain the autosomal and X-linked forms of Alport syndrome (AS), and a subset of thin basement membrane nephropathy (TBMN). A number of X-linked AS patients follow a milder course reminiscent of that of patients with heterozygous COL4A3/COL4A4 mutations and TBMN, while at the same time a significant subset of patients with TBMN and familial MH progress to chronic kid...

Genetic renal abnormalities

Medicine — Wed, 25 May 2011 21:24:39 +0100

Abstract: Inherited disorders of renal structure and function are relatively common causes of end-stage renal disease requiring renal replacement therapy. A family history of haematuria, urinary tract infection or renal failure can alert the clinician to the possible diagnosis of underlying renal genetic abnormalities. In practice, the commonest inherited renal disorder is autosomal dominant polycystic kidney disease (ADPKD), characterized by multiple kidney cysts associated with hypertension and renal failure. Insights into the cell biology of ADPKD are informing new therapeutic approaches to limit cyst growth and prevent progressive renal failure. Non-visible haematuria is a clinical finding that presents a diagnostic challenge because it has so many possible causes. Mutations in the gen...

Glomerular pathology in Alport syndrome: a molecular perspective

Pediatric Nephrology — Thu, 31 Mar 2011 17:40:22 +0100

Abstract We have known for some time that mutations in the genes encoding 3 of the 6 type IV collagen chains are the underlying defect responsible for both X-linked (where the COL4A5 gene is involved) and autosomal (where either COL4A3 or COL4A4 genes are involved) Alport syndrome. The result of these mutations is the absence of the sub-epithelial network of all three chains in the glomerular basement membrane (GBM), resulting, at maturity, in a type IV collagen GBM network comprising only α1(IV) and α2(IV) chains. The altered GBM functions adequately in early life. Eventually, there is onset of proteinuria associated with the classic and progressive irregular thickening, thinning, and splitting of the GBM, which culminates in end-stage renal failure. We have learned muc...

Women and Alport syndrome

Pediatric Nephrology — Fri, 04 Mar 2011 16:46:59 +0100

Abstract X-linked Alport syndrome (XLAS) is caused by mutations in type IV collagen causing sensorineural hearing loss, eye abnormalities, and progressive kidney dysfunction that results in near universal end-stage renal disease (ESRD) and the need for kidney transplantation in affected males. Until recent decades, the disease burden in heterozygous “carrier” females was largely minimized or ignored. Heterozygous females have widely variable disease outcomes, with some affected females exhibiting normal urinalysis and kidney function, while others develop ESRD and deafness. While the determinants of disease severity in females with XLAS are uncertain, skewing of X-chromosome inactivation has recently been found to play a role. This review will explore the natural histor...

Alport syndrome and leiomyomatosis: the first deletion extending beyond COL4A6 intron 2

Pediatric Nephrology — Fri, 04 Mar 2011 16:46:59 +0100

Abstract Alport syndrome (ATS) is a nephropathy characterized by the association of progressive hematuric nephritis with ultrastructural changes of the glomerular basement membrane (thinning, thickening, and splitting), sensorineural deafness, and variable ocular abnormalities (anterior lenticonus, macular flecks, and cataracts). The most common mode of transmission is X-linked inheritance, due to COL4A5 mutations. X-linked ATS is rarely associated with diffuse leiomyomatosis (DL), a benign hypertrophy of the visceral smooth muscle in gastrointestinal, respiratory, and female reproductive tracts. The ATS-DL complex is due to deletions that encompass the 5′ ends of the COL4A5 and COL4A6 genes and include the bidirectional promoter. In this paper, we described 3 ATS-DL case...

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Biophysical properties of normal and diseased renal glomeruli

AJP: Cell Physiology — Mon, 28 Feb 2011 00:00:00 +0100

The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to 1,400 Pa by blebbistatin. Cytochalasin or latrunculin reduced the F/G actin ratios of glomeruli but did not disrupt their architecture. To assess glomerular ...

Pulmonary outcome of alport syndrome with familial diffuse esophageal leiomymatosis

Pediatric Pulmonology — Mon, 31 Jan 2011 00:00:00 +0100

We describe herein, the pulmonary complications and outcome of three family members (mother, daughter and son). The three underwent esophagectomy at different age (22 years, three years and 15 months respectively). Their current forced expiratory volume in the first second (FEV1) range from 33% in the mother to 60% in the daughter and 97% in the son. It is suggested that earlier intervention may lead to improved pulmonary function tests. Pediatr. Pulmonol. © 2011 Wiley‐Liss, Inc. (Source: Pediatric Pulmonology)

Mapping structural landmarks, ligand binding sites, and missense mutations to the collagen IV heterotrimers predicts major functional domains, novel interactions, and variation in phenotypes in inherited diseases affecting basement membranes

Human Mutation — Fri, 28 Jan 2011 21:42:46 +0100

AbstractCollagen IV is the major protein found in basement membranes. It comprises three heterotrimers (α1α1α2, α3α4α5, and α5α5α6) that form distinct networks, and are responsible for membrane strength and integrity. We constructed linear maps of the collagen IV heterotrimers (“interactomes”) that indicated major structural landmarks, known and predicted ligand‐binding sites, and missense mutations, in order to identify functional and disease‐associated domains, potential interactions between ligands, and genotype–phenotype relationships. The maps documented more than 30 known ligand‐binding sites as well as motifs for integrins, heparin, von Willebrand factor (VWF), decorin, and bone morphogenetic protein (BMP). They predicted functional domains for angiogenesis and ...

Glomerular basement membrane disorders in experimental models for renal diseases: impact on understanding pathogenesis and improving diagnosis.

Contributions to Nephrology — Sun, 23 Jan 2011 00:30:15 +0100

Authors: Kashtan CE, Segal Y Animal models have provided important insights into human renal diseases that arise from mutations in genes that encode or regulate the synthesis of glomerular basement membrane proteins. This chapter describes several well-characterized animal models of type IV collagen disorders (Alport syndrome, HANAC syndrome), a laminin disorder (Pierson syndrome), nail-patella syndrome and HERNS syndrome. These models can be exploited in studies of the pathogenesis and treatment of such disorders. PMID: 21252518 [PubMed - in process] (Source: Contributions to Nephrology)

Ten-Year Retrospective Analysis of Incisional Herniorrhaphy Following Renal Transplantation [Original Article]

Archives of Surgery — Mon, 17 Jan 2011 00:00:00 +0100

Conclusions To our knowledge, this is the largest series of incisional herniorrhaphies performed among patients following renal transplantation. Although smoking history, the presence of diabetes, and immunosuppressive therapy were not associated with the initial development of an incisional hernia, they were associated with complications. Component separation performed by transplant and plastic and reconstructive surgeons should be considered in the setting of recurrent hernias and large defects. (Source: Archives of Surgery)

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Biophysical Properties of Normal and Diseased Renal Glomeruli.

Am J Physiol Cell Ph... — Wed, 01 Dec 2010 00:00:00 +0100

Authors: Wyss HM, Henderson JM, Byfield FJ, Bruggeman LA, Ding Y, Huang C, Suh JH, Franke T, Mele E, Pollak MR, Miner JH, Janmey PA, Weitz DA, Miller RT The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury, but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to...

Mapping structural landmarks, ligand binding sites and missense mutations to the collagen IV heterotrimers predicts major functional domains, novel interactions and variation in phenotypes in inherited diseases affecting basement membranes

Human Mutation — Thu, 18 Nov 2010 00:00:00 +0100

AbstractCollagen IV is the major protein found in basement membranes. It comprises 3 heterotrimers (α1α1α2, α3α4α5, and α5α5α6) that form distinct networks, and are responsible for membrane strength and integrity. We constructed linear maps of the collagen IV heterotrimers (‘interactomes’) that indicated major structural landmarks, known and predicted ligand‐binding sites, and missense mutations, in order to identify functional and disease‐associated domains, potential interactions between ligands, and genotype‐phenotype relationships. The maps documented more than 30 known ligand‐binding sites as well as motifs for integrins, heparin, von Willebrand factor (VWF), decorin and bone morphogenetic protein (BMP). They predicted functional domains for angiogenesis and haemo...

Aortic abnormalities in males with Alport syndrome

Nephrology Dialysis Transplantation — Mon, 18 Oct 2010 23:00:00 +0100

Conclusions. Early onset aortic disease may be an unusual feature of AS. Screening of men with AS for aortic abnormalities may be clinically indicated in some families. (Source: Nephrology Dialysis Transplantation)

Clonal overgrowth of esophageal smooth muscle cells in diffuse leiomyomatosis-Alport syndrome caused by partial deletion in COL4A5 and COL4A6 genes.

Matrix Biology — Tue, 12 Oct 2010 23:00:00 +0100

Authors: Oohashi T, Naito I, Ueki Y, Tomoki Y, Tanaka PR, Yoshio N, Ninomiya Y This is a study of a patient who manifests all of the features of a diffuse leiomyomatosis-Alport syndrome (DL-ATS), and her two-year-old son who has already been diagnosed with Alport syndrome. Fourteen years ago, the patient underwent a partial esophageal resection followed by a replacement with jejunum. Recently, she underwent a surgical resection of the esophagus due to esophageal dysfunction. Genetic analyses of COL4A5 and COL4A6 on the X-chromosome were efficiently performed using the genomic DNA of her son. We have identified a novel deletion of 194-kb in length, encompassing COL4A5-COL4A6 promoters as well as nearly the entire large intron 1 of COL4A5 and intron 2 of COL4A6. To uncover the relationsh...

Ventricular septal defect in a child with Alport syndrome: a case report

BMC Cardiovascular Disorders — Mon, 04 Oct 2010 23:00:00 +0100

Conclusions: This first report of a cardiovascular association highlights the possible involvement of collagen mutations in the two pathologies. Even when drug-resistance appears to be responsible for the failure to control secondary hypertension in AS, clonidine may represent a safe, effective option in the normalization of high blood pressure. (Source: BMC Cardiovascular Disorders)

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Mutation detection of COL4An gene based on mRNA of peripheral blood lymphocytes and prenatal diagnosis of Alport syndrome in China

Nephrology — Fri, 01 Oct 2010 00:00:00 +0100

Conclusion: An easier, faster and efficacious method for COL4An gene mutation screening based on mRNA analysis from peripheral blood lymphocytes was established. Prenatal genetic diagnosis was performed in four AS families in China. (Source: Nephrology)

The Value of Clinical Criteria in Identifying Patients with X-Linked Alport Syndrome.

Clinical Journal of the American Society of Nephrology : CJASN — Wed, 29 Sep 2010 23:00:00 +0100

CONCLUSIONS: The authors recommend COL4A5 analysis in any patient meeting at least two clinical diagnostic criteria. COL4A3 and COL4A4 analysis should be considered if a COL4A5 mutation is not detected and primarily if autosomal inheritance is suspected. PMID: 20884774 [PubMed - as supplied by publisher] (Source: Clinical Journal of the American Society of Nephrology : CJASN)

Collagen XIII Induced in Vascular Endothelium Mediates {alpha}1{beta}1 Integrin-Dependent Transmigration of Monocytes in Renal Fibrosis.

Am J Pathol — Wed, 22 Sep 2010 23:00:00 +0100

In this study, we report the identification of collagen XIII as a ligand that facilitates this selective recruitment of Î±1Î²1 integrin-positive monocytes. Collagen XIII is absent in the vascular endothelium from normal renal cortex and abundant in Alport renal cortex. Neutralizing antibodies against the binding site in collagen XIII for Î±1Î²1 integrin selectively block VLA1-positive monocyte migration in transwell assays. Injection of these antibodies into Alport mice slows monocyte recruitment and protects against renal fibrosis. Thus, the induction of collagen XIII in endothelial cells of Alport kidneys mediates the selective recruitment of Î±1Î²1 integrin-positive monocytes and may potentially serve as a therapeutic target for inflammatory diseases in which lymphocyte/mono...

Molecular Architecture of the Goodpasture Autoantigen in Anti-GBM Nephritis

New England Journal of Medicine — Tue, 20 Jul 2010 23:00:00 +0100

This study compared the conformation of the antibody epitopes in Goodpasture's disease and Alport's post-transplantation nephritis in search of the pathogenesis of anti-basement membrane glomerulonephritis. The authors report evidence that the initiation of such disease depends on the conformation involving perturbation of the quaternary structure of basement-membrane collagen, eliciting an autoimmune response. (Source: New England Journal of Medicine)

The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney

Nephrology Dialysis Transplantation — Fri, 16 Jul 2010 20:16:16 +0100

Conclusions. The present study shows that the increased glomerular permeability and the subsequently altered megalin-mediated and megalin-dependent cubilin-mediated endocytosis lead to a partial LMW proteinuria and partial HMW proteinuria. (Source: Nephrology Dialysis Transplantation)

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Ultrasound: A Helpful Diagnostic Tool in Esophageal Leiomyomatosis with Alport Syndrome.

Ultraschall in der Medizin — Tue, 06 Jul 2010 23:00:00 +0100

Authors: Denne C, Hahn H, Steinborn M, Hosie S, Lenz JC, HÃ¶pner F, Burdach S PMID: 20614415 [PubMed - as supplied by publisher] (Source: Ultraschall in der Medizin)

Trypsin Digestion on Paraffin Sections Is a Useful Tool for Diagnosis of Alport Syndrome.

Ultrastructural Pathology — Sun, 04 Jul 2010 19:45:29 +0100

Authors: Jiang YS, Ehara T Trypsin digestion for 90 min revealed the alpha(5) chain of type IV collagen along the glomerular basement membrane and Bowman's capsule in paraffin-embedded renal sections of controls. In the 9 patients with the ultrastructures suggestive of Alport syndrome (AS), 8 patients were classified as X-linked dominant type due to the lack or mosaic pattern of alpha(5) chain in paraffin sections of renal biopsies by trypsin digestion, and 1 patient was classified as autosomol recessive type due to the lack of alpha(5) chain in the glomerular basement membrane only. Trypsin digestion is useful for the diagnosis of AS in paraffin-embedded renal tissue. PMID: 20594039 [PubMed - as supplied by publisher] (Source: Ultrastructural Pathology)

Pattern of glomerular diseases in Sudanese children:A clinico-pathological study.

Saudi Journal of Kidney Diseases and Transplantation — Wed, 30 Jun 2010 23:00:00 +0100

Authors: Abdelraheem MB, Ali el-TM, Mohamed RM, Hassan EG, Abdalla OA, Mekki SO, Yousif BM, Watson AR Glomerular diseases are a common cause of chronic kidney disease (CKD) in many countries. The pattern of glomerular diseases has been reported in adult Sudanese patients but there has been no previous study on Sudanese children. The aim of this study is to describe the pattern of glomerular diseases in Sudanese children from a clinico-pathological perspective. We retrospectively reviewed the clinical records of 321 children seen with nephritis/nephrosis at the Pediatric Nephrology Unit, Soba University Hospital and Dr. Salma Dialysis and Kidney Transplantation Centre, Khartoum, Sudan during the period from 2002 to 2007. Biopsies were studied with light microscopy and immuno-histochemis...

The Alport syndrome COL4A5 variant database

Human Mutation — Wed, 23 Jun 2010 23:00:00 +0100

Alport Syndrome is a progressive renal disease with cochlear and ocular involvement. The most common form ([sim]80%) is inherited in an X-linked pattern. X-linked Alport Syndrome (XLAS) is caused by mutations in the type IV collagen alpha chain 5 (COL4A5). We have developed a curated disease-specific database containing reported sequence variants in COL4A5. Currently the database archives a total of 520 sequence variants, verified for their position within the COL4A5 gene and named following standard nomenclature. Sequence variants are reported with accompanying information on protein effect, classification of mutation vs. polymorphism, mutation type based on the first description in the literature, and links to pertinent publications. In addition, features of this database include disease...

An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review.

Clinical Nephrology — Fri, 28 May 2010 16:15:22 +0100

Authors: Joosten H, Strunk AL, Meijer S, Boers JE, AriÃ«s MJ, Abbes AP, Engel H, Beukhof JR Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these disorders. As a guideline to differential diagnosis, we provide an overview of the clinical manifestations and the pathogenesis of the main genetic disorders with chronic renal insufficiency surfacing in adulthood and add an algorithm plus 4 tables. We also indicate where molecular genetics nowadays can be of aid in the diagnostic process. The following disorders are discussed by mode of inheritance: 1) A...

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Wavefront analysis and Scheimpflug imagery in diagnosis of anterior lenticonus

Journal of Cataract and Refractive Surgery — Fri, 30 Apr 2010 23:00:00 +0100

We present the case of an Alport syndrome patient whose anterior lenticonus was detected by wavefront analysis and Scheimpflug imaging technology. The patient's lenticular abnormalities were too subtle to be detected by the initial slitlamp examination. Normal corneal topography and elevation maps with high total-eye aberrations pointed to internal optics as the source of aberrations, and predominant negative spherical aberrations suggested anterior lenticonus, a diagnosis confirmed by Scheimpflug images that showed central bulging of the anterior lens surface. Following diagnosis, uneventful phacoemulsification and intraocular lens implantation were performed. We recommend wavefront analysis and Scheimpflug imaging technology as effective tools in the detection of lens disorders, especial...

Severe Alport syndrome in a young woman caused by a t(X;1)(q22.3;p36.32) balanced translocation

Pediatric Nephrology — Mon, 12 Apr 2010 17:47:31 +0100

We examined the molecular mechanism of development of the disease in a female patient with severe Alport syndrome. The patient showed heavy proteinuria, hematuria, neurosensory hearing loss and primary amenorrhea. Renal biopsy findings of electron microscopy and immunostaining of the α5 chain of type IV collagen indicated a female X-linked Alport syndrome. G-banding chromosomal analysis showed a t(X;1)(q22.3;p36.32) balanced translocation. Analysis of the collagen type IV (COL4A5) gene by genomic DNA sequencing, complementary DNA (cDNA) sequencing and multiplex ligation-dependent probe amplification assay showed no mutations or deletions/duplications of the gene. However, fluorescence in situ hybridization using the probes for exon 1 and exon 51 of the COL4A5 gene showed disruption o...

Primary renal disease in young adults with renal failure

Nephrology Dialysis Transplantation — Fri, 26 Mar 2010 09:54:47 +0100

Conclusions. These young adult data in the UK are consistent with the hypothesis that many of the undiagnosed cases must be CAKUT or tubular disease. (Source: Nephrology Dialysis Transplantation)

Haemovigilance for the optimal use of blood products in the hospital

Vox Sanguinis — Sun, 21 Mar 2010 00:00:00 +0100

(Source: Vox Sanguinis)

Loss of collagen-receptor DDR1 delays renal fibrosis in hereditary type IV collagen disease.

Matrix Biology — Fri, 19 Mar 2010 00:00:00 +0100

Authors: Gross O, Girgert R, Beirowki B, Kretzler M, Kang HG, Kruegel J, Miosge N, Busse AC, Segerer S, Vogel WF, Müller GA, Weber M Alport syndrome is a hereditary type IV collagen disease leading progressive renal fibrosis, hearing loss and ocular changes. End stage renal failure usually develops during adolescence. COL4A3 -/- mice serve as an animal model for progressive renal scarring in Alport syndrome. The present study evaluates the role of Discoidin Domain Receptor 1 (DDR1) in cell-matrix-interaction involved in pathogenesis of Alport syndrome including renal inflammation and fibrosis. DDR1/COL4A3 double-knockouts were compared to COL4A3 -/- mice with 50% or 100% expression of DDR1, wildtype controls and to DDR1-/- COL4A3 +/+ controls for over 6 years. Double-knockouts liv...

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Cyclosporine A treatment in patients with Alport syndrome: a single-center experience

Pediatric Nephrology — Thu, 18 Mar 2010 15:24:50 +0100

Abstract Limited and discordant data are available on cyclosporine A (CsA) treatment for proteinuria in Alport syndrome (AS). To address this lack of consistent data, we have studied 15 AS patients (14 males; mean age 15.3 ± 6.0 years) treated with CsA. Patient selection criteria included a urinary protein/creatinine ratio ≥1 mg/mg and a creatinine clearance >40 ml/min/1.73 m2. CsA treatment was started at an initial dose of 5 mg/kg/day and subsequently adjusted to reach target C2 levels of 500 ng/ml. Renal function, proteinuria, and blood pressure were monitored. Blood pressure was treated to avoid the administration of angiotensin converting enzyme or angiotensin receptor blockers for the first 2 years of therapy. The average fo...

Bilateral vocal cord paralysis in a patient with chronic renal failure associated with Alport syndrome

Journal of Anesthesia — Thu, 11 Mar 2010 02:41:20 +0100

Abstract A 61-year-old woman with chronic renal failure (CRF) associated with Alport syndrome underwent coronary artery aneurysmectomy under general anesthesia. Hemorrhage control was difficult during the surgery, and she became hemodynamically unstable. The surgery and anesthesia lasted 446 and 552 min, respectively. On postoperative day 1, she developed severe respiratory distress several minutes after extubation. Her trachea was immediately reintubated. The second attempt to extubate her trachea also failed. Fiberoptic examination revealed bilateral vocal cord paralysis (VCP) due to recurrent laryngeal nerve (RLN) paralysis. Although she needed a temporary tracheostomy, vocal cord movement recovered without treatment 3 months after surgery. The mechanisms unde...

Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome

Journal of Clinical Investigation — Tue, 02 Mar 2010 17:25:43 +0100

The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization–associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3–/– mice, which model Alport syndrome. Ablation of Usag1 in Col4a3–/– mice led to substantial attenuation of disease progression, normalization of GBM...

Non-immunologic mechanisms of calcineurin inhibitors explain its antiproteinuric effects in genetic glomerulopathies

Pediatric Nephrology — Tue, 02 Mar 2010 10:01:42 +0100

Abstract It has been reported (this issue Pediatric Nephrology) that cyclosporine A (CyA) therapy in combination with corticosteroids, angiotensin-converting enzyme inhibitor, and an angiotensin receptor blocker decreased proteinuria in three patients with nephrotic syndrome (NS) due to WT1 mutations. Treatment with calcineurin inhibitors were found to induce a partial remission of proteinuria in several other children with genetic forms of NS, such as mutation in the podocine and in the phospholipase C epsilon gene. CyA therapy has also been reported to be beneficial to patients with Alport syndrome. Recent data have shown that the antiproteinuric effect of CyA in these cases may be due to a non-immunologic mechanism. CyA exerts an antiproteinuria effect by preventing the d...

Retinal Basement Membrane Abnormalities and the Retinopathy of Alport Syndrome [Retina]

Investigative Ophthalmology — Fri, 26 Feb 2010 01:05:10 +0100

Alport syndrome results in the thinning of both the internal limiting membrane and Bruch's membrane in the retina. The dot-and-fleck retinopathy corresponds to hyperreflectivity of the internal limiting membrane/nerve fiber layer, and the lozenge and macular hole correspond to temporal macular thinning. (Source: Investigative Ophthalmology)

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X-inactivation modifies disease severity in female carriers of murine X-linked Alport syndrome

Nephrology Dialysis Transplantation — Thu, 25 Feb 2010 08:19:38 +0100

Conclusions. Our findings establish X-inactivation as a major modifier of the carrier phenotype in X-linked Alport syndrome. Thus, X-inactivation patterns may offer prognostic information and point to possible treatment strategies for symptomatic carriers. (Source: Nephrology Dialysis Transplantation)

Novel heterozygous COL4A3 mutation in a family with late-onset ESRD

Pediatric Nephrology — Tue, 23 Feb 2010 07:40:56 +0100

We report an Italian family who presented with hematuria and mild proteinuria. Mutational analysis showed a novel heterozygous mutation p.G291E in exon 15 of the COL4A3 gene. Many different mutations in COL4A3 and COL4A4 that cause TBMN have already been identified, but most genetic variability in these genes has been found to cause autosomal ATS. A valid genotype–phenotype correlation for TBMN or ATS is not yet known. Therefore, it is important to identify new mutations by direct sequencing to clarify their clinical importance, to assess the prognosis of the disease, and to avoid renal biopsy. Content Type Journal ArticleCategory Brief ReportDOI 10.1007/s00467-010-1467-4Authors Julia Hoefele, University Children’s Hospital, Ludwig-Maximilian’s University Pediatric Nephrolo...

Journal Of Clinical Investigation Online News Feb. 8, 2010

Urology / Nephrology News From Medical News Today — Tue, 09 Feb 2010 12:00:00 +0100

NEPHROLOGY: New approach to treating the kidney disease Alport syndrome? Alport syndrome is a progressive hereditary kidney disease with no definitive therapy. It is caused by mutations in any of the collagen IV genes (COL4A3, COL4A4, and COL4A5)... (Source: Urology / Nephrology News From Medical News Today)

JCI online early table of contents: Feb. 8, 2010

EurekAlert! - Medicine and Health — Mon, 08 Feb 2010 05:00:00 +0100

(Journal of Clinical Investigation) This release contains summaries, links to PDFs, and contact information for the following newsworthy papers to be published online, Feb. 8, 2010, in the JCI: Marker of Ewing sarcoma: potential new drug target?; Enhancing arrest of cell growth to treat cancer in mice; New approach to treating the kidney disease Alport syndrome?; Role for the protein HIF-2-alpha in Chuvash polycythemia; Rab25: a suppressor of tumor formation in intestines?; and Complete chemokine profile of a cell. (Source: EurekAlert! - Medicine and Health)

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Mutant-type α5(IV) collagen in a mild form of Alport syndrome has residual ability to form a heterotrimer

Pediatric Nephrology — Wed, 03 Feb 2010 17:56:10 +0100

Abstract Alport syndrome (AS) is caused by mutations in type IV collagen α3, α4, and α5 chains. The three chains form a heterotrimer. We have previously shown that all 15 types of recombinant α5(IV) chains with mutations, corresponding to AS mutations, in the noncollagenous (NC1) domain are defective in terms of heterotrimer formation and/or secretion of the heterotrimer from cells. A relatively large family with Cys1638Tyr in the NC1 domain of the α5(IV) chain has been found to have mild AS phenotypes without hearing loss or ocular abnormalities. Renal biopsies of different family members also revealed the presence of the α3(IV), α4(IV), and α5(IV) chains in the glomerular basement membrane. In our study, we introduced the mutation corresponding to Cys1638Tyr into...

West Nile virus in 2006 and 2007: the Canadian Blood Services' experience.

Transfusion — Tue, 29 Dec 2009 00:00:00 +0100

CONCLUSION: WNV-positive donations correspond geographically with the epidemic. MP testing identifies most potentially infectious donations with a smaller potential benefit from targeted ID-NAT. Mild symptoms are common but may not deter donation. PMID: 20051051 [PubMed - as supplied by publisher] (Source: Transfusion)

Ocular abnormalities in Alport syndrome

Journal of Cataract and Refractive Surgery — Wed, 23 Dec 2009 14:48:40 +0100

Seymenoğlu and Baser state that the ocular abnormalities in Alport syndrome, such as glomerular lesions, result from a defect common to the formation of both basement membranes. However, it should be “renal” rather than “ocular” abnormalities. Gregory et al. proposed diagnostic criteria for Alport syndrome. As described in their , at least 4 of 10 criteria must be met. There is no need for the presence of ocular lesions to diagnose Alport syndrome. (Source: Journal of Cataract and Refractive Surgery)

Alport syndrome: significance of gingival biopsy in the initial diagnosis and periodontal evaluation after renal transplantation

Journal of Applied Oral Science — Mon, 21 Dec 2009 13:58:50 +0100

Alport Syndrome (AS) is an important hereditary disorder affecting the glomerular basement membrane. Diagnosis of AS is based on the presence of hematuric nephropathy, renal failure, hearing loss, ocular abnormalities and changes in the glomerular basement membrane of the lamina densa. The aims of this case report were to show the changes in the gingival tissues in a patient with AS under therapy with cyclosporin-A after renal transplantation and to discuss the possible role of type IV collagen in gingival basal lamina as an alternative approach for the diagnosis of AS. A 20-year-old male patient with AS underwent periodontal therapy including a series of gingivectomy surgeries. Gingival samples obtained during the second surgery were examined histopathologically and by transmission electr...

Interstitial inflammation in Alport syndrome

Human Pathology — Fri, 11 Dec 2009 00:00:00 +0100

Summary: The Alport syndrome is a hereditary glomerular disease linked to structural abnormalities of collagen IV. In a mouse model of Alport syndrome, the interstitial lymphocyte influx was important for disease progression. CXCR3 is a chemokine receptor involved in lymphocyte recruitment to the kidney. We hypothesized that CXCR3-positive T cells might be involved in human Alport syndrome. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded biopsies from 17 patients with Alport syndrome, 10 with immunoglobulin A (IgA) nephropathy, and 11 healthy donor kidneys. We investigated the expression of the α5 chain of collagen IV to confirm the morphologic diagnosis, the chemokine receptor CXCR3 and CD3-positive T cells. Alport syndrome biopsies demonstrated a complete loss of...

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Alport Retinopathy Results from "Severe" COL4A5 Mutations and Predicts Early Renal Failure.

Clinical Journal of the American Society of Nephrology : CJASN — Thu, 03 Dec 2009 00:00:00 +0100

CONCLUSIONS: Severe mutations in male individuals with X-linked Alport syndrome are associated with the perimacular dot-and-fleck retinopathy. Furthermore, the retinopathy indicates that male individuals are at increased risk for renal failure before the age of 30 (P = 0.0007). PMID: 19965530 [PubMed - as supplied by publisher] (Source: Clinical Journal of the American Society of Nephrology : CJASN)

Retinal findings in patients with Alport Syndrome: expanding the clinical spectrum

British Journal of Ophthalmology — Wed, 25 Nov 2009 18:06:24 +0100

Conclusions: Patients with AS can present with a variety of ophthalmic manifestations. Bull’s eye maculopathy and vitelliform deposits can be features of AS. The mechanism of these new macular findings remains unknown. Possible pathophysiological overlap with other maculopathies including age-related macular degeneration is discussed. (Source: British Journal of Ophthalmology)

A family with X-linked benign familial hematuria

Pediatric Nephrology — Tue, 24 Nov 2009 07:09:56 +0100

Abstract Gene mutations in COL4A5 located on Xq22 are believed to cause X-linked Alport syndrome, whereas mutations in COL4A3 and COL4A4 located on chromosome 2 are associated with autosomal inherited Alport syndrome or benign familial hematuria. A family with benign familial hematuria caused by COL4A5 mutation, implying X-linked transmission, is reported here for the first time. This result suggests that COL4A5 should be added to the list of causative genes for benign familial hematuria, although the mechanism(s) by which the same mutation leads to the distinct phenotypes, i.e. X-linked Alport syndrome or benign familial hematuria, remains unknown. Content Type Journal ArticleCategory Brief ReportDOI 10.1007/s00467-009-1370-zAuthors Kazunari Kaneko, Kansai Medical Univer...

Alport Syndrome - Facts and Information

Disabled World — Sat, 21 Nov 2009 19:40:06 +0100

Alport syndrome is a form of genetic disease involving a mutation that affects a person’s ears, eyes and kidneys. The syndrome is named for Doctor Alport, who described a British family whose members developed both deafness and renal disease in the year 1927. (Source: Disabled World)

Molecular testing for adult type Alport syndrome

BioMed Central — Tue, 17 Nov 2009 00:00:00 +0100

Conclusions: This test may be useful for presymptomatic and carrier testing in families with one of the mutations and in the diagnosis of unexplained hematuria or chronic kidney disease. (Source: BioMed Central)

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Pregnancy complicated with Alport syndrome: A good obstetric outcome and failure to diagnose an infant born to a mother with Alport syndrome by umbilical cord immunofluorescence staining

Journal of Obstetrics and Gynaecology Research — Mon, 09 Nov 2009 00:00:00 +0100

We report a primigravida with Alport syndrome with mild proteinuria who gave birth abdominally to a term male infant without deteriorating renal function during pregnancy. The umbilical cord from not only this infant but also from an Alport (-) control infant showed negative immunofluorescence staining for the alpha 5 chain of type IV collagen. Women with Alport syndrome without renal dysfunction may follow an uneventful obstetrical course until term. The cord may not be suitable for diagnosing Alport syndrome with immunofluorescence staining. (Source: Journal of Obstetrics and Gynaecology Research)

18F-fluorodeoxyglucose PET/CT in a patient with esophageal and genital leiomyomatosis.

Korean J Radiol — Sun, 01 Nov 2009 00:00:00 +0100

Authors: An YS, Kim DY Diffuse esophageal leiomyomatosis is a rare benign tumor, which can be associated with leiomyoma in female genital tracts involving the uterus, vagina, and vulva. Alport syndrome, an inherited disorder that includes the kidneys, eyes, and sensorineural hearing loss, is also rarely associated with these multiple leiomyomatosis. In our case, (18)F-fluorodeoxyglucose positron emission tomography/computed tomography was used to distinguish esophageal and genital leiomyomatosis from malignant masses. PMID: 19885320 [PubMed - in process] (Source: Korean J Radiol)

Drugs controlling proteinuria of patients with Alport syndrome.

World Journal of Pediatrics : WJP — Sun, 01 Nov 2009 00:00:00 +0100

CONCLUSIONS: ACEI is effective in controlling proteinuria of AS patients. Tripterygium should be carefully administered in controlling proteinuria of AS patients. PMID: 19911149 [PubMed - in process] (Source: World Journal of Pediatrics : WJP)

Unravelling the genetic basis of renal diseases; from single gene to multifactorial disorders

The Journal of Pathology — Sat, 31 Oct 2009 00:00:00 +0100

Chronic kidney disease is common with up to 5% of the adult population reported to have an estimated glomerular filtration rate of < 60 ml/min/1.73 m2. A large number of pathogenic mutations have been identified that are responsible for 'single gene' renal disorders, such as autosomal dominant polycystic kidney disease and X-linked Alport syndrome. These single gene disorders account for < 15% of the burden of end-stage renal disease that requires dialysis or kidney transplantation. It has proved more difficult to identify the genetic susceptibility underlying common, complex, multifactorial kidney conditions, such as diabetic nephropathy and hypertensive nephrosclerosis. This review describes success to date and explores strategies currently employed in defining the genetic basis for a nu...

Epstein syndrome with rapid progression to end stage renal disease.

Saudi Journal of Kidney Diseases and Transplantation — Fri, 30 Oct 2009 10:08:36 +0100

Authors: Alhindawi E, Al-Jbour S The association of haematological abnormalities and hereditary nephritis is rare; it is mainly included in a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly, Fechtner, Sebastian, Epstein and Alport syndrome with macro thrombocytopenia. We are presenting a missed case of a boy who presented with epistaxis and his diagnostic work up revealed macrothrombocytopenia, sensorineural hearing loss and chronic nephropathy which constitute the Epstein syndrome, with rapid deterioration of kidney function. PMID: 19861875 [PubMed - in process] (Source: Saudi Journal of Kidney Diseases and Transplantation)

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Alport's syndrome.

Saudi Journal of Kidney Diseases and Transplantation — Fri, 30 Oct 2009 10:08:24 +0100

Authors: Oni AO, Eweka AO, Otuaga PO, Odia JO PMID: 19861880 [PubMed - in process] (Source: Saudi Journal of Kidney Diseases and Transplantation)

Stem Cells Offer New Hope For Kidney Disease Patients

ScienceDaily Headlines — Fri, 23 Oct 2009 21:00:00 +0100

Several cell-based therapy approaches could provide new treatments for patients with Alport syndrome, according to a new study. (Source: ScienceDaily Headlines)

Cell-Based Therapies May Be Beneficial in Alport Syndrome

Modern Medicine — Thu, 15 Oct 2009 23:00:00 +0100

Cell-based therapies may offer hope to patients with Alport syndrome, according to an animal study published online Oct. 15 in the Journal of the American Society of Nephrology. (Source: Modern Medicine)

Analysis of the Glomerular Basement Membrane in Images of Renal Biopsies Using the Split-and-Merge Method: A Pilot Study

Journal of Digital Imaging — Thu, 17 Sep 2009 12:42:09 +0100

Abstract Abnormal thinning, thickening, or variation in the thickness of the glomerular basement membrane (GBM) are caused by familial hematuria, diabetes mellitus, and Alport syndrome, respectively. We propose a semi-automated procedure for the segmentation and analysis of the thickness of the GBM in images of renal biopsy samples obtained by using a transmission electron microscope (TEM). The procedure includes the split-and-merge algorithm, morphological image processing, skeletonization, and statistical analysis of the width of the GBM. The procedure was tested with 34 TEM images of six patients. The mean and standard deviation of the GBM width for a patient with normal GBM were estimated to be 368 ± 177 nm, those for a patient with thin GBM associated with f...

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CKD in MYH9-Related Disorders

American Journal of Kidney Diseases — Wed, 02 Sep 2009 23:00:00 +0100

MYH9-related disorders are rare causes of chronic kidney disease (CKD) presenting as chronic glomerulonephritis and derive from mutations of the MYH9 gene, which encodes for the nonmuscle myosin heavy chain IIA. These disorders are autosomal dominant and include May-Hegglin anomaly and Sebastian, Fechtner, and Epstein syndromes. Diagnosis of these disorders is made first in early childhood because of the characteristic peripheral-blood smear findings of thrombocytopenia, giant platelets, and variably detected basophilic cytoplasmic inclusion bodies in leukocytes. CKD typically develops later in adulthood and may progress to end-stage renal disease. MYH9-related disorders may be associated with deafness and cataract; hence, Alport syndrome becomes important in the differential diagnosis. Ho...

A rare case of MYH9 disorders presenting with macrothrombocytopenia and deafness caused by MYH9-R702C mutation

Thrombosis Research — Mon, 31 Aug 2009 23:00:00 +0100

Giant platelets often appear in acquired thrombocytopenia, such as idiopathic thrombocytopenic purpura (ITP) and myelodysplastic syndrome1. Congenital macrothrombocytopenia is rare, and consists of a variety of diseases , including 4 autosomal dominant disorders, May-Hegglin anomaly, and Sebastian, Fechtner, and Epstein syndromes, which have neutrophil inclusion bodies (Döhle-like bodies), or Alport-like symptoms (nephritis, deafness, or cataract) . These diseases have been differentiated by expression pattern and morphology of neutrophil inclusion bodies, or the clinical features of Alport-like manifestations . Mutations of the non-muscle myosin heavy chain 9 (MYH9) gene which encodes non-muscle myosin heavy chain IIA (NMMHC-IIA), however, were identified in all 4 disorders . From this v...

Clinico-pathological correlations in 127 patients in 11 large pedigrees, segregating one of three heterozygous mutations in the COL4A3/ COL4A4 genes associated with familial haematuria and significant late progression to proteinuria and chronic kidney disease from focal segmental glomerulosclerosis

Nephrology Dialysis Transplantation — Sun, 16 Aug 2009 23:00:00 +0100

Conclusions. Our data confirm for the first time a definite association of heterozygous COL4A3/COL4A4 mutations with familial microscopic haematuria, thin basement membrane nephropathy and the late development of familial proteinuria, CRF, and ESRD, due to FSGS, indicating that the term ‘benign familial haematuria’ is a misnomer, at least in this cohort. A strong hypothesis for a causal relationship between these mutations and FSGS is also made. Benign familial haematuria may not be so benign as commonly thought. (Source: Nephrology Dialysis Transplantation)

Anesthetic management of a patient with Alport-leiomyomatosis syndrome

Journal of Anesthesia — Fri, 14 Aug 2009 18:29:48 +0100

We report the anesthetic management of esophagectomy for a patient with Alport-leiomyomatosis syndrome. A 23-year-old woman complained of dysphagia and severe chest pain. Her chest X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) showed an enlarged esophagus, in contact with the trachea, heart, aorta, and large vessels. She frequently experienced severe asthma attacks. Because various risks in both respiration and circulation, especially in anesthesia induction, were of concern, her right femoral vessels were exposed, for the emergency use of percutaneous cardiopulmonary support (PCPS), prior to anesthesia induction. Anesthesia was induced and maintained with propofol, fentanyl, and vecuronium. Esophagectomy was performed uneventfully and no severe events were se...

Postrenal biopsy AVM leading to severe hypertension and dilated cardiomyopathy

Pediatric Nephrology — Mon, 03 Aug 2009 20:45:45 +0100

Abstract A 3-year-old girl with Alport syndrome presented with decompensated heart failure from hypertension-induced cardiomyopathy 6 months following renal biopsy. Selective renal angiography revealed a large left renal arteriovenous fistula (AVF) with poor perfusion to the left renal parenchyma. The AVF was treated by transcatheter embolization using an Amplatzer vascular plug. Her blood pressure normalized after embolization, and her cardiac function normalized over the following 4 months. Content Type Journal ArticleCategory Brief ReportDOI 10.1007/s00467-009-1268-9Authors Nao Sasaki, Division of Pediatric Cardiology Mount Sinai Medical Center One Gustave L. Levy Place New York NY 10029 USAUmesh C. Joashi, Division of Pediatric Cardiology Mount Sinai Medica...

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Retinal Findings in Patients with Alport Syndrome: Expanding the Clinical Spectrum.

The British Journal of Ophthalmology — Sat, 25 Jul 2009 23:00:00 +0100

CONCLUSIONS: Patients with AS can present with a variety of ophthalmic manifestations. Bull's eye maculopathy and vitelliform deposits can be features of AS. The mechanism of these new macular findings remains unknown. Possible pathophysiologic overlap with other maculopathies including age-related macular degeneration is discussed. PMID: 19635720 [PubMed - as supplied by publisher] (Source: The British Journal of Ophthalmology)

[Unclear deterioration of vison after renal transplant.]

Der Ophthalmologe — Wed, 08 Jul 2009 23:00:00 +0100

Authors: Hild M, Walter HS, Milioti G, Seitz B A 27-year-old female patient reported a variable but unsatisfactory visual acuity which had persisted for several years. The patient had been dependent on dialysis from the age of 14 years old and from then on also needed a hearing aid. A kidney had been transplanted 5 years ago. The diagnosis was anterior lenticonus due to Alport syndrome. PMID: 19585124 [PubMed - as supplied by publisher] (Source: Der Ophthalmologe)

Childhood primary glomerular diseases in the western region of Saudi Arabia.

Saudi Journal of Kidney Diseases and Transplantation — Tue, 30 Jun 2009 23:00:00 +0100

We report our institute experience on primary glomerular disease in children in the western region of Saudi Arabia over the last 18 years (1988 to 2006). A total of 169 cases were identified as primary glomerular diseases in children and adolescent with age range from first year of life till 18 years. Minimal change disease and focal segmental glomerulosclerosis were the com-monly encountered primary glomerular diseases (20.1%and 19.5% respectively), mesangioprolifera-tive glomerulonephritis IgM nephropathy (14.8%), IgA nephropathy (10.7%), postinfectious glome-rulonephritis (9.5%), membranous glomerulonephritis (7.1%), membranoproliferative glomerulone-phritis (5.9%) and mesangioproliferative glomerulonephritis with negative immunofluorescence (5.9%). The less frequently encountered prima...

Ocular manifestations and surgical results in patients with Alport syndrome

Journal of Cataract and Refractive Surgery — Thu, 25 Jun 2009 08:03:24 +0100

We report the ocular manifestations of Alport syndrome and the surgical results in 4 patients. All 4 patients had anterior lenticonus; 2 also had posterior lenticonus in both eyes, 3 had flecked retina, and 1 had posterior polymorphous dystrophy. In both eyes of the 4 patients, phacoemulsification with intraocular lens (IOL) implantation was performed to treat anterior and posterior lenticonus. The postoperative visual acuity was excellent in all patients. We recommend phacoemulsification with IOL implantation as a safe and effective procedure in patients with lenticonus secondary to Alport syndrome. (Source: Journal of Cataract and Refractive Surgery)

Oculoleptomeningeal amyloidosis in 3 individuals with the transthyretin variant Tyr69His.

Canadian Journal of Ophthalmology — Sun, 31 May 2009 23:00:00 +0100

CONCLUSIONS: This report adds to the literature regarding OLMA and its association with a Tyr69His mutation in the TTR gene. Despite no proven therapy at this time, symptomatic treatment with pars plana vitrectomy appears to be beneficial. PMID: 19491989 [PubMed - in process] (Source: Canadian Journal of Ophthalmology)

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Array-CGH in unclear syndromic nephropathies identifies a microdeletion in Xq22.3-q23

Pediatric Nephrology — Fri, 15 May 2009 05:54:13 +0100

Abstract To investigate whether submicroscopic chromosomal deletions or duplications can be causative of unclear syndromic nephropathies, we analyzed ten patients with congenital abnormalities of the kidney and urinary tract or glomerulopathies combined with important extrarenal anomalies by whole-genome array-based comparative genomic hybridization. In a 14-year-old girl presenting with hematuria, proteinuria, mental retardation (MR), sensorineural hearing loss, dysmorphisms, and epilepsy, we detected a microdeletion in chromosome Xq22.3-q23. This deletion was verified and characterized by fluorescence in situ hybridization and multiplex ligation-dependent probe amplification analyses, found to be de novo, uniallelic and 3.3 Mb in size. Electron microscopy of a kidne...

Identification of novel variants in the COL4A4 gene in Korean patients with thin basement membrane nephropathy.

The Indian Journal of Medical Research — Thu, 30 Apr 2009 23:00:00 +0100

CONCLUSION: The frequency of COL4A4 mutations in Korean patients with TBMN is low and the other cases may have mutations in other genes like COL4A3. Screening of the COL4A3 gene and finding a novel causative gene for TBMN will help clarify the pathogenesis of this disorder and perhaps for distinguishing TBMN from Alport syndrome. PMID: 19675380 [PubMed - in process] (Source: The Indian Journal of Medical Research)

Women with Alport syndrome: risks and rewards of kidney donation

Nephrology Dialysis Transplantation — Tue, 14 Apr 2009 04:00:00 +0100

(Source: Nephrology Dialysis Transplantation)

Autosomal dominant Alport syndrome: molecular analysis of the COL4A4 gene and clinical outcome

Nephrology Dialysis Transplantation — Tue, 14 Apr 2009 04:00:00 +0100

Conclusions. These data indicate autosomal dominant Alport syndrome as a disease with a low risk of ocular and hearing anomalies but with a significant risk to develop renal failure although at an older age than the X-linked form. We were unable to demonstrate a genotype–phenotype correlation. Altogether, these data make difficult the differential diagnosis with the benign familial haematuria due to heterozygous mutations of COL4A4 and COL4A3, especially in young patients, and with the X-linked form of Alport syndrome in families where only females are affected. A correct diagnosis and prognosis is based on a comprehensive clinical investigation in as many family members as possible associated with a broadly formal genetic analysis of the pedigree. (Source: Nephrology Dialysis Transp...

Living donor kidney transplantation from relatives with mild urinary abnormalities in Alport syndrome: long-term risk, benefit and outcome

Nephrology Dialysis Transplantation — Tue, 14 Apr 2009 04:00:00 +0100

Conclusion. Living donor Tx from relatives in Alport families is an ambivalent option. Proteinuria should be an exclusion criterion. Yet, even in donors with isolated microhaematuria, families and their physicians should be aware of an increased risk of renal failure in donor and recipient. This risk might be minimized by careful donor evaluation including biopsy and nephroprotective strategies after Tx in both donor and recipient. (Source: Nephrology Dialysis Transplantation)

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Development of lupus nephritis is associated with qualitative changes in the glomerular collagen IV matrix composition.

Lupus — Sun, 15 Mar 2009 15:10:10 +0100

Authors: Tveita A, Ninomiya Y, Sado Y, Rekvig O, Zykova S Lupus nephritis is associated with thickening of the glomerular extracellular membranes. Distribution of collagen IV alpha-chains in the glomerular basement membrane in kidneys of lupus-prone B/W mice has been examined in this study. The results are indicative of a qualitative change in the collagen IV matrix occurring around the time of development of proteinuria, with an embryonic alpha1/alpha2 isoform replacing the normal glomerular basement membrane (GBM). These changes mimic alterations seen in Alport syndrome and coincide with an increase in collagenolytic activity within the glomerulus. It has been hypothesized that alterations in collagen matrix synthesis represent compensatory responses to an increase in GBM proteolysis...

Atypical Alport syndrome associated with a novel COL4A5 mutation.

Clinical Nephrology — Sun, 01 Mar 2009 05:00:00 +0100

Authors: Höpker K, Liebau MC, Friederichsohn C, Waldherr R, Benzing T Alport syndrome is a progressive hereditary renal disease. Mutations in the genes encoding for three members of the type IV collagen protein family have been found to be the cause of the disease. Alport syndrome is often associated with sensorineural hearing loss and ocular abnormalities, and patients suffering from typical Alport syndrome usually develop end stage renal disease during adolescence or young adulthood. Here we report on a family with atypical Alport disease initially presenting as hereditary focal and segmental glomerulosclerosis. Genetic testing identified a previously undescribed COL4A5 mutation as cause of the disease. PMID: 19281745 [PubMed - in process] (Source: Clinical Nephrology)

Disease recurrence in paediatric renal transplantation

Pediatric Nephrology — Fri, 27 Feb 2009 13:52:45 +0100

Abstract Renal transplantation (Tx) is the treatment of choice for end-stage renal disease. The incidence of acute rejection after renal Tx has decreased because of improving early immunosuppression, but the risk of disease recurrence (DR) is becoming relatively high, with a greater prevalence in children than in adults, thereby increasing patient morbidity, graft loss (GL) and, sometimes, mortality rate. The current overall graft loss to DR is 7–8%, mainly due to primary glomerulonephritis (70–80%) and inherited metabolic diseases. The more typical presentation is a recurrence of the full disease, either with a high risk of GL (focal and segmental glomerulosclerosis 14–50% DR, 40–60% GL; atypical haemolytic uraemic syndrome 20–80% DR, 10–83% GL; membranoprolife...

Patterns of primary glomerular diseases among adults in the western region of Saudi Arabia.

Saudi Journal of Kidney Diseases and Transplantation — Thu, 26 Feb 2009 21:42:42 +0100

In conclusion this study demonstrates that MGN is the most common primary GN encountered in the studied cases, the second more frequent is FSGSC. This result is in contrast to previous reports from Saudi Arabia where MGN is reported with low frequency and FSGSC is reported the most common primary GN. PMID: 19237826 [PubMed - in process] (Source: Saudi Journal of Kidney Diseases and Transplantation)

[Original articles] The dot-and-fleck retinopathy of X linked Alport syndrome is independent of complement factor H (CFH) gene polymorphisms

British Journal of Ophthalmology — Tue, 24 Feb 2009 05:00:00 +0100

Conclusion: The pathogenesis of the retinal dots and flecks in Alport syndrome is independent of CFH-dependent mechanisms and, like other clinical features, may depend on the nature of the underlying COL4A5 mutations. (Source: British Journal of Ophthalmology)

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[Original articles] The retinal "lozenge" or "dull macular reflex" in Alport syndrome may be associated with a severe retinopathy and early-onset renal failure

British Journal of Ophthalmology — Tue, 24 Feb 2009 05:00:00 +0100

Conclusion: Clinicians must be aware that the "lozenge" or "dull macular reflex" described in Alport syndrome is not a normal variant but reflects a severe, almost confluent perimacular dot and fleck retinopathy. This sign is useful diagnostically and also prognostically, since it is associated with early-onset renal failure. (Source: British Journal of Ophthalmology)

Stem cell therapy for Alport syndrome: the hope beyond the hype

Nephrology Dialysis Transplantation — Wed, 18 Feb 2009 05:00:00 +0100

(Source: Nephrology Dialysis Transplantation)

Alport syndrome and thin glomerular basement membrane nephropathy: a practical approach to diagnosis.

Archives of Pathology and Laboratory Medicine — Sun, 01 Feb 2009 05:00:00 +0100

CONCLUSIONS: Although Alport syndrome variants and TBMN do not show characteristic light microscopic findings and can be difficult to differentiate from each other even by electron microscopy, using a combination of electron microscopy and immunohistology for alpha(3)(IV) and alpha(5)(IV) enables pathologists to definitively diagnose these disorders on renal biopsy in most cases. PMID: 19195966 [PubMed - in process] (Source: Archives of Pathology and Laboratory Medicine)

Detection by multiplex ligation-dependent probe amplification of large deletion mutations in the COL4A5 gene in female patients with Alport syndrome

Pediatric Nephrology — Sat, 24 Jan 2009 12:39:48 +0100

Content Type Journal ArticleCategory Letter to the EditorsDOI 10.1007/s00467-009-1122-0Authors Kandai Nozu, Kobe University Graduate School of Medicine Department of Pediatrics Kusunokicho 7-5-1, Chuo Kobe 650-0017 Hyogo JapanRafal Przybyslaw Krol, Kobe University Graduate School of Medicine Department of Pediatrics Kusunokicho 7-5-1, Chuo Kobe 650-0017 Hyogo JapanKoichi Nakanishi, Wakayama Medical University Department of Pediatrics Wakayama JapanNorishige Yoshikawa, Wakayama Medical University Department of Pediatrics Wakayama JapanYoshimi Nozu, Kobe University Graduate School of Medicine Department of Pediatrics Kusunokicho 7-5-1, Chuo Kobe 650-0017 Hyogo JapanYasufumi Ohtsuka, Saga Medical School Department of Pediatrics Saga JapanKazumoto Iijima, Kobe University Graduate School of...

Identification of the first in cis mutations in MYH9 disorder

European Journal of Haematology — Tue, 13 Jan 2009 05:00:00 +0100

Here, we report the first in cis mutations in exon 1 of the MYH9 gene in a patient with MYH9 disorder. The patient was a 5-yr-old girl with macrothrombocytopenia and conspicuous cytoplasmic inclusion bodies in neutrophils. Immunofluorescence analysis of neutrophil non-muscle myosin heavy chain-II A (NMMHC-IIA) indicated several cytoplasmic spots of NMMHC-IIA aggregates that were circular to oval in shape (type II pattern). Mutational analysis showed two mutations, c.99G > T and c.103C > G, which would result in p.W33C and p.P35A, respectively, in exon 1 of the MYH9 gene. In addition, concurrent mutations were present on the same chromosome. Inclusion bodies are usually faint or mostly invisible in MYH9 disorders with a mutation in exon 1. In this case, double mutations might have caused th...

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[Glycobiology and Extracellular Matrices] Identification of Noncollagenous Sites Encoding Specific Interactions and Quaternary Assembly of {alpha}3{alpha}4{alpha}5(IV) Collagen: IMPLICATIONS FOR ALPORT GENE THERAPY

Journal of Biological Chemistry — Fri, 05 Dec 2008 05:00:00 +0100

Defective assembly of 345(IV) collagen in the glomerular basement membrane causes Alport syndrome, a hereditary glomerulonephritis progressing to end-stage kidney failure. Assembly of collagen IV chains into heterotrimeric molecules and networks is driven by their noncollagenous (NC1) domains, but the sites encoding the specificity of these interactions are not known. To identify the sites directing quaternary assembly of 345(IV) collagen, correctly folded NC1 chimeras were produced, and their interactions with other NC1 monomers were evaluated. All 1/5 chimeras containing 5NC1 residues 188-227 replicated the ability of 5NC1 to bind to 3NC1 and co-assemble into NC1 hexamers. Conversely, substitution of 5NC1 residues 188-227 by 1NC1 abolished these quaternary interactions. The amino-termina...

The dot and fleck retinopathy of X-linked Alport sydnrome is independent of complement factor H (CFH) gene polymorphisms.

The British Journal of Ophthalmology — Wed, 19 Nov 2008 05:00:00 +0100

CONCLUSION: The pathogenesis of the retinal dots and flecks in Alport syndrome is independent of CFH-dependent mechanisms and, like other clinical features, may depend on the nature of the underlying COL4A5 mutations. PMID: 19019939 [PubMed - as supplied by publisher] (Source: The British Journal of Ophthalmology)

The retinal 'lozenge' or 'dull macular reflex' in Alport syndrome is associated with a severe retinopathy and early onset renal failure.

The British Journal of Ophthalmology — Wed, 19 Nov 2008 05:00:00 +0100

CONCLUSION: Clinicians must be aware the 'lozenge' or 'dull macular reflex' described in Alport syndrome is not a normal variant but reflects a severe almost confluent perimacular dot and fleck retinopathy. This sign is useful diagnostically and also prognostically since it is associated with early onset renal failure. PMID: 19019929 [PubMed - as supplied by publisher] (Source: The British Journal of Ophthalmology)

Severe to profound hearing loss in patients with progressed Alport's syndrome.

Acta Oto-Laryngologica — Tue, 18 Nov 2008 05:00:00 +0100

Conclusion: The concept of hearing loss severity must be redefined, as there is a clear need for more active hearing management in Alport's syndrome patients with severe and profound hearing loss. Objectives: Sensorineural hearing loss (SNHL) caused by Alport's syndrome generally does not exceed 60-70 dB, because a cochlear lesion is responsible for this hearing loss. Careful management of renal function improves the prognosis and the longevity of Alport's syndrome patients; it is useful to reassess SNHL caused by Alport's syndrome. Patients and methods: Thirty-two patients with Alport's syndrome were analyzed retrospectively. Pure tone audiograms (PTAs), speech audiograms, and transiently evoked otoacoustic emissions (TEOAEs) were performed. Hearing loss severity was compared to duration ...

Development of nucleic Acid transfection technology to the kidney.

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan — Sat, 01 Nov 2008 04:00:00 +0100

Authors: Mukai H, Kawakami S, Hashida M The kidney is one of the most important organs that play a crucial role in homeostasis and, therefore, congenital or acquired renal dysfunction causes refractory diseases, i.e., Alport's syndrome, Fabry's disease, diabetic nephropathy, IgA nephropathy, kidney cancer, transplant glomerulopathy. Nucleic acid transfection technology to the kidney is indispensable for the progress of biomedical research and the realization of gene therapy and nucleic acid drug for renal diseases. Control of renal nucleic acid transfection was difficult because of the structural complexity; however, the study of recombinant virus, synthetic carrier and physical force-mediated nucleic acid transfection to the kidney has advanced. Recombinant virus and synthetic carrier...

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[Development of nucleic acid transfection technology to the kidney]

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan — Sat, 01 Nov 2008 04:00:00 +0100

Antigen retrieval with protease digestion applied in immunohistochemical diagnosis of Alport syndrome

Nephrology Dialysis Transplantation — Wed, 15 Oct 2008 04:00:00 +0100

Conclusions. Compared to the autoclave heating method, protease antigen retrieval is more convenient and effective and can be used to restore type IV collagen chains on paraffin-embedded renal sections for the diagnosis of AS. (Source: Nephrology Dialysis Transplantation)

Deletion of Cd151 Results in a Strain-Dependent Glomerular Disease Due to Severe Alterations of the Glomerular Basement Membrane.

The American Journal of Pathology — Thu, 11 Sep 2008 04:00:00 +0100

In conclusion, CD151 appears to be involved in the establishment, maturation, and/or maintenance of the GBM structure in addition to its role in integrin-mediated adhesion strengthening. PMID: 18787104 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)

Cryoprecipitate use in 25 Canadian hospitals: commonly used outside of the published guidelines.

Transfusion — Thu, 28 Aug 2008 04:00:00 +0100

CONCLUSION: A 2-month audit of cryoprecipitate use in Canada revealed that the majority of cryoprecipitate use in Canada is not in accordance with published guidelines. PMID: 18764824 [PubMed - as supplied by publisher] (Source: Transfusion)

The R229Q mutation in NPHS2 may predispose to proteinuria in thin-basement-membrane nephropathy

Pediatric Nephrology — Tue, 26 Aug 2008 07:57:02 +0100

Abstract Thin-basement-membrane nephropathy (TBMN) is characterized by persistent dysmorphic hematuria, and the presence of proteinuria is a risk factor for renal impairment. TBMN is often due to mutations in the COL4A3 and COL4A4 genes, and this study determined whether additional mutations in genes encoding other structures in the glomerular filtration barrier contributed to the development of proteinuria. Fifty-six unrelated individuals with TBMN including 18 (32%) with proteinuria ≥ 300 mg/L and ten (18%) with proteinuria ≥ 500 mg/L were studied. Deoxyribonucleic acid (DNA) was screened for NPHS2 mutations and variants (R138Q and P375L) using single-stranded conformational analysis (SSCA) and for the R229Q mutation by sequencing. DNA was also screened for A...

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Clinical and Genetic Mapping of X Chromosome in the X-linked Dominant Inherited Alport's syndrome.

Saudi Journal of Kidney Diseases and Transplantation — Wed, 20 Aug 2008 13:24:21 +0100

Authors: Dai Y, Huang Y, He X, Wang S, Huang R, Tang M, Hu C To study the hereditary mode and clinical characteristics and detect mutations of gene COL4A5 encoding type IV collagen a5 chain among family members of an X-linked dominant inherited Alport's syndrome (AS) family of China, we studied all of 38 family members of whom 2 volunteers underwent renal biopsy. Genomic DNA from all members of the AS family was characterized. All of 51 exons of COL4A5 gene were amplified by polymerase chain reaction (PCR) with the primers synthesized according to the published flanking intervening sequences. PCR products were further analyzed by agarose gel electrophoresis and single strand conformation polymorphism (SSCP) analysis. The study subjects revealing polymorphism by SSCP analysis were direc...

Somatic mosaicism for a mutation of the COL4A5 gene is a cause of mild phenotype male Alport syndrome

Nephrology Dialysis Transplantation — Mon, 28 Jul 2008 04:00:00 +0100

Conclusions. Our findings indicate that somatic mosaicism for COL4A5 is responsible for male X-linked Alport syndrome with an 5 mosaic staining pattern. Several cases with somatic mosaicism have previously been reported, however, this is the first case where the presence of this mutation was proved with a comprehensive analysis of genomic DNA, mRNA and 5 expression in the tissues. Somatic mosaicism may thus be one of the causes of the mild phenotype in Alport syndrome. (Source: Nephrology Dialysis Transplantation)

Detection of large deletion mutations in the COL4A5 gene of female Alport syndrome patients

Pediatric Nephrology — Fri, 27 Jun 2008 06:52:06 +0100

This report concerns two female patients with X-linked Alport syndrome. Although mutational analysis of the COL4A5 gene was conducted with direct sequencing using genomic DNA and mRNA extracted from leukocytes, the results were negative for detection of mutations. Semi-quantitative PCR using genomic DNA was therefore conducted to detect large heterozygous deletions. The results were that the first patient showed complete loss of the COL4A5 gene and the second patient showed deletion from exons 37 to 51. Our patients possessed large heterozygous deletions in the COL4A5 gene that could not be detected with the standard direct sequencing method and were identified with semi-quantitative PCR. Previously reported mutation detection rates for female patients have been lower than overall rat...

MLPA and cDNA analysis improves COL4A5 mutation detection in X-linked Alport syndrome.

Clinical Genetics — Thu, 26 Jun 2008 04:00:00 +0100

Authors: Hertz J, Juncker I, Marcussen N The X-linked form of Alport syndrome (AS) is caused by mutations in the COL4A5 gene encoding the alpha5 chain of type IV collagen. Most COL4A5 mutations are individual, and mutation analysis is complicated by the size of the gene and the number of exons. Larger structural rearrangements account for 10-15% of mutations. We have established a method for mutation analysis of COL4A5 based on reverse transcriptase-polymerase chain reaction analysis of mRNA from cultured skin fibroblasts and multiplex ligation-dependent probe amplification (MLPA) on genomic DNA. One advantage of using skin biopsies for the mRNA analysis is the possibility of immunohistochemical staining for the alpha5(IV) chain on skin sections to support a diagnosis of X-linked AS. A...

A primer on recurrent and de novo glomerulonephritis in renal allografts.

Nature Clinical Practice. Nephrology. — Tue, 17 Jun 2008 04:00:00 +0100

Authors: Ivanyi B Accumulating evidence indicates that recurrent glomerulonephritis is the third most important cause of renal allograft loss at 10 years after transplantation. The proteinuria and elevated serum creatinine levels that result from recurrent glomerulonephritis are associated with cardiovascular morbidity and mortality. The exact prevalence of either recurrent or de novo post-transplantation glomerulonephritis is unknown because a considerable number of patients never undergo allograft biopsy, meaning that glomerulonephritis remains undiagnosed and a diagnosis of 'chronic rejection/chronic allograft nephropathy' is sometimes presumed. The lack of consensus regarding evaluation of kidney transplant recipients who exhibit slow deterioration of graft function is a major reas...

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Diffuse alveolar hemorrhage following alemtuzumab.

Chest — Sun, 01 Jun 2008 04:00:00 +0100

This study describes an unusual patient with X-linked Alport syndrome (XLAS) in whom diffuse alveolar hemorrhage (DAH) developed as a complication of alemtuzumab therapy following renal transplantation. A 26-year-old man with XLAS underwent retransplantation with a cadaveric renal allograft. He received alemtuzumab therapy as a part of an immunosuppressive induction protocol, and dyspnea and hemoptysis developed. A chest CT scan showed diffuse alveolar opacities. Bronchoscopy was performed to determine the cause of hemoptysis and hypoxia. BAL showed a characteristic increasingly bloody return in the sequential aliquots. There was no growth of pathogenic bacteria or evidence of opportunistic infection. Clinical improvement occurred with the initiation of steroids, and the patient required s...

[Collagen alpha5 and alpha2 (IV) chain coexpression: The procedure of choice to diagnose Alport syndrome from skin biopsies.]

Annales de Pathologie — Sun, 01 Jun 2008 04:00:00 +0100

We describe a simple procedure to use skin biopsies for the diagnosis of Alport syndrome. The technique is based on the codetection of alpha5 and alpha2 chains of collagen IV along the basal lamina of epidermis through an immunfluorescence technique. Eighty-five per cent of the cases of Alport syndrome are due to a mutation in the gene COL4A5, located on chromosome X, encoding the alpha5 chain of collagen IV. In this situation, the tissue expression of alpha5 chain is abnormal; in males, the absence of expression of alpha5 chain is pathognomonic for Alport syndrome; in females, the expression of alpha5 chain may be discontinuous because of X inactivation. The alpha2 chain is used as a positive control. We have studied skin biopsies from 55 patients (35 females, 20 males) with a suspicion o...

[Collagen alpha5 and alpha2 (IV) chain coexpression: The procedure of choice to diagnose Alport syndrome from skin biopsies]

Annales de Pathologie — Sun, 01 Jun 2008 04:00:00 +0100

We describe a simple procedure to use skin biopsies for the diagnosis of Alport syndrome. The technique is based on the co-detection of alpha5 and alpha2 chains of collagen IV along the basal lamina of epidermis through an immunfluorescence technique. Eighty-five per cent of the cases of Alport syndrome are due to a mutation in the gene COL4A5, located on chromosome X, encoding the alpha5 chain of collagen IV. In this situation, the tissue expression of alpha5 chain is abnormal; in males, the absence of expression of alpha5 chain is pathognomonic for Alport syndrome; in females, the expression of alpha5 chain may be discontinuous because of X inactivation. The alpha2 chain is used as a positive control. We have studied skin biopsies from 55 patients (35 females, 20 males) with a suspicion ...

Clear lens phacoemulsification in anterior lenticonus due to Alport Syndrome: two case reports

BioMed Central — Tue, 27 May 2008 04:00:00 +0100

Conclusion: All four eyes of the two patients were in good condition after surgery and achieved satisfactory optical and visual results and had no remarkable complications at six-months follow-up. Clear lens phacoemulsification with foldable intraocular lens implantation can be used as an efficient and safe procedure for vision disorders in these patients. (Source: BioMed Central)

[ARTICLES] Sequence dependence of kinetics and morphology of collagen model peptide self-assembly into higher order structures

Protein Science — Tue, 27 May 2008 04:00:00 +0100

The process of self-assembly of the triple-helical peptide (Pro-Hyp-Gly)10 into higher order structure resembles the nucleation-growth mechanism of collagen fibril formation in many features, but the irregular morphology of the self-assembled peptide contrasts with the ordered fibers and networks formed by collagen in vivo. The amino acid sequence in the central region of the (Pro-Hyp-Gly)10 peptide was varied and found to affect the kinetics of self-assembly and nature of the higher order structure formed. Single amino acid changes in the central triplet produced irregular higher order structures similar to (Pro-Hyp-Gly)10, but the rate of self-association was markedly delayed by a single change in one Pro to Ala or Leu. The introduction of a Hyp-rich hydrophobic sequence from type IV col...

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Novel COL4A3 mutations in African American siblings with autosomal recessive Alport syndrome.

American Journal of Kidney Diseases — Sat, 26 Apr 2008 19:33:27 +0100

We describe a novel mutational study in 2 African American siblings with autosomal recessive Alport syndrome. Both siblings were compound heterozygotes for 2 abnormal DNA sequences in exon 49 of the COL4A3 gene, p.Arg1496X (CGA-->TGA) and p.Arg1516X (CGA-->TGA). These are nonsense mutations in the noncollagenous domain resulting in premature termination codons and have not been previously reported. In an African American population in which autosomal recessive Alport syndrome is rarely seen, complete sequencing of the COL4A3 and COL4A4 genes may be necessary to identify the underlying mutation and confirm the diagnosis. PMID: 18436078 [PubMed - in process] (Source: American Journal of Kidney Diseases)

[ARTICLES] Sequence dependence of kinetics and morphology of collagen model peptide self-assembly into higher order structures

Protein Science — Fri, 25 Apr 2008 04:00:00 +0100

The process of self-assembly of the triple-helical peptide (Pro-Hyp-Gly)10 into higher order structure resembles the nucleation-growth mechanism of collagen fibril formation in many features, but the irregular morphology of the self-assembled peptide contrasts with the ordered fibers and networks formed by collagen in vivo. The amino acid sequence in the central region of the (Pro-Hyp-Gly)10 peptide was varied and found to affect the kinetics of self-assembly and nature of the higher order structure formed. Single amino acid changes in the central triplet produced irregular higher order structures similar to (Pro-Hyp-Gly)10,, but the rate of self-association was markedly delayed by a single change in one Pro to Ala or Leu. The introduction of a Hyp-rich hydrophobic sequence from type IV co...

Prenatal Diagnosis and Genetic Counseling of a Chinese Alport Syndrome Kindred

Genetic Testing — Fri, 28 Mar 2008 13:19:54 +0100

Genetic Testing Mar 2008, Vol. 12, No. 1: 1-7. Alport syndrome (AS) is a progressive renal disease characterized by hematuria and progressive renal failure. X-linked dominant AS (XLAS) is the major inheritance form, accounting for almost 80% of the cases, caused by mutations in COL4A5 gene. An ... (Source: Genetic Testing)

The use of ocular abnormalities to diagnose X-linked Alport syndrome in children

Pediatric Nephrology — Sat, 15 Mar 2008 09:14:46 +0100

Abstract The diagnosis of X-linked Alport syndrome is often difficult, but the demonstration of lenticonus and retinopathy may facilitate the diagnosis in adult patients. The aim of this study was to determine the diagnostic usefulness of ocular examination in children. Fourteen families with at least one affected child were studied clinically, and COL4A5 mutations were determined. The families included 15 affected boys (median age 11 years, range 4–19 years). Two boys (13%) had renal failure, nine (60%) had a known hearing loss, one (7%) had lenticonus and five (33%) had a central (4/15, 27%) or peripheral (4/14, 29%) retinopathy. Lenticonus and retinopathy were first noted in 14 and 11 year olds, respectively. All boys with retinopathy had a hearing loss. The ...

Urine erythrocyte morphology in patients with microscopic haematuria caused by a glomerulopathy

Pediatric Nephrology — Fri, 07 Mar 2008 06:51:22 +0100

Abstract The evaluation of urinary erythrocyte morphology (UEM) has been proposed for patients with isolated microscopic haematuria (IMH) to early orientate the diagnosis towards a glomerular or a nonglomerular disease. However, to date, the role of this test in patients with IMH has very rarely been investigated. Sixteen patients (ten children, six adults) with persistent IMH classified as glomerular on the basis of repeated UEM evaluations (55 urine samples, two to eight per patient) were submitted to renal biopsy. This showed a glomerular disease in 14/16 patients (87.5%) (nine thin basement membrane disease; three Alport syndrome; two other), whereas in two patients, no abnormalities were found. Of four microscopic criteria investigated to define a IMH as glomerular, &...

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Correction: Sefer et al: Effects of Renal Transplantation on Hearing and Ocular Changes in a Monozygotic Twin with Alport's Syndrome: Comparison with Other Twin on Hemodialysis.

Croatian Medical Journal — Fri, 01 Feb 2008 05:00:00 +0100

Authors: Degoricija V PMID: 18293454 [PubMed - in process] (Source: Croatian Medical Journal)

Mammalian collagen IV

Microscopy Research and Technique — Thu, 24 Jan 2008 05:00:00 +0100

Four decades have passed since the first discovery of collagen IV by Kefalides in 1966. Since then collagen IV has been investigated extensively by a large number of research laboratories around the world. Advances in molecular genetics have resulted in identification of six evolutionary related mammalian genes encoding six different polypeptide chains of collagen IV. The genes are differentially expressed during the embryonic development, providing different tissues with specific collagen IV networks each having unique biochemical properties. Newly translated [alpha]-chains interact and assemble in the endoplasmic reticulum in a chain-specific fashion and form unique heterotrimers. Unlike most collagens, type IV collagen is an exclusive member of the basement membranes and through a compl...

Alport Syndrome and Pregnancy.

Obstetric Anesthesia Digest — Fri, 18 Jan 2008 09:33:16 +0100

Page: 214DOI: 10.1097/01.aoa.0000302327.98527.75 (Source: Obstetric Anesthesia Digest)

A familial case of mitochondrial disease resembling Alport syndrome

Clinical and Experimental Nephrology — Tue, 08 Jan 2008 16:29:09 +0100

Abstract A 38-year-old man with mild sensorineural hearing loss, diabetes mellitus, proteinuria, and slight renal dysfunction was admitted to our hospital for a renal biopsy to determine the cause of kidney disease. His elder sister and mother also had sensorineural hearing loss and renal failure, suggesting the existence of a common genetic disease in this family. Although the clinical features of the patient were similar to features of Alport syndrome, renal biopsy revealed no sign of Alport syndrome. We next considered a possibility of a mitochondrial kidney disease described by Jansen in 1997. Indeed, genetic analysis of mitochondrial DNA clarified the existence of A3243G mutation in the patient and his sister. This syndrome should be recognized by nephrologists as a d...

Lymphocytes are dispensable for glomerulonephritis but required for renal interstitial fibrosis in matrix defect-induced Alport renal disease

Laboratory Investigation AOP — Mon, 07 Jan 2008 05:00:00 +0100

Authors: Valerie S LeBleu, Hikaru Sugimoto, Caroline A Miller, Vincent H Gattone & Raghu Kalluri (Source: Laboratory Investigation AOP)

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Inherited diseases of the glomerular basement membrane.

Nature Clinical Practice. Nephrology. — Tue, 01 Jan 2008 05:00:00 +0100

Authors: Gubler MC The glomerular basement membrane (GBM) is a specialized form of basement membrane that has a major role in the maintenance of the glomerular filtration barrier. Like all basement membranes, it contains four main components: type IV collagen, laminin, nidogen, and heparan sulfate proteoglycans. Different isoforms of these large molecules are produced. These isoforms have a tissue-specific distribution; in the mature GBM, the major type IV collagen molecule is the alpha 3 alpha 4 alpha 5(IV) isoform, associated with laminin-521 (alpha 5 beta2 gamma 1), nidogen and agrin heparan sulfate proteoglycans. The importance of the GBM has been demonstrated by identification of hereditary glomerular diseases linked to structural anomalies of its components; for example, type IV ...

Acute Rejection Rates and Survival of Renal Transplant Recipients With Alport's Syndrome.

Transplantation Proceedings — Tue, 01 Jan 2008 05:00:00 +0100

In conclusion, although the number of patients in our series was small, in light of their uneventful postoperative periods and the good posttransplantation renal function in our recipients, we consider Alport's syndrome recipients as good candidates for transplantation. PMID: 18261563 [PubMed - in process] (Source: Transplantation Proceedings)

Mutational analysis of type IV collagen alpha5 chain, with respect to heterotrimer formation.

Biochemical and Biophysical Research communications — Thu, 13 Dec 2007 05:00:00 +0100

In this study, we introduced 12 kinds of missense and three kinds of nonsense mutations, corresponding to AS mutations, into the NC1 domain of alpha5(IV) and characterized the mutant chains. Nine alpha5(IV) chains with amino acid substitutions and all three truncated alpha5(IV) chains did not form a heterotrimer and were not secreted from cells. Three alpha5(IV) chains with amino acid substitutions did, however, form heterotrimers in cells, but these were not secreted from cells. These findings indicate that a defect in heterotrimer formation is the main molecular mechanism underlying the pathogenesis of AS caused by mutation in the NC1 domain. We also showed that even a single amino acid deletion in the carboxyl-terminal region markedly affected the heterotrimerization, indicating that th...

Why Are My Baby's Eyes Dancing?

PediatricEducation.org — Tue, 04 Dec 2007 01:46:57 +0100

Discussion Children should be screened for visual problems from birth onwards. Asking the parent whether they have any vision concerns may elicit the first clue to uncovering an abnormality. From birth until 2 years infants and toddler should have the following eye evaluation: Examination of the eyelids, conjunctiva, sclera, cornea and iris, pupils, and eyelids. Corneal light reflexes can evaluate muscle balance, ocular motility, and acuity. The symmetry of the corneal light reflexes on the pupil when the eye is fixed and when the eyes are in motion are noted. The light reflex should be symmetrical at all times; if it is not, then a referral to ophthalmology should be made. Unilateral cover test - must be performed with the eyes fixated on an object. The first eye is then covered while th...

Alport Syndrome With Recurrent Herpes Simplex Virus Keratitis.

Cornea — Wed, 28 Nov 2007 01:32:35 +0100

Page: 1279DOI: 10.1097/ICO.0b013e31814da529Authors: Chung, Pei-Chen MD; Lin, Ken-Kuo MD; Song, Hu-Shien MD; Ku, Wan-Chen MD; Huang, Samuel C M MD; Sun, Chi-Chin MD, PhD (Source: Cornea)

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Type VII collagen in Alport syndrome

Nephrology Dialysis Transplantation — Tue, 27 Nov 2007 05:00:00 +0100

Conclusions. Our results indicate that lack of 5(IV) molecule significantly alters the assembly of extracellular matrix molecules other than x(IV) chains also at the EBM level. We suggest that the increased synthesis and deposition of type VII collagen is likely to balance the absence of stabilizing activity normally exerted by 5(IV). (Source: Nephrology Dialysis Transplantation)

A Novel Mutation of COL4A3 Presents a Different Contribution to Alport Syndrome and Thin Basement Membrane Nephropathy

American Journal of Nephrology — Tue, 09 Oct 2007 12:55:48 +0100

Am J Nephrol 2007;27:538-544 (DOI:10.1159/000107666) (Source: American Journal of Nephrology)

Familial hematuria

Pediatric Nephrology — Wed, 03 Oct 2007 16:36:32 +0100

Abstract Hematuria is a common presenting complaint in pediatric nephrology clinics and often has a familial basis. This teaching article provides an overview of causes, diagnosis, and management of the major forms of familial hematuria, Alport syndrome, and thin basement membrane nephropathy. Content Type Journal ArticleCategory Educational FeatureDOI 10.1007/s00467-007-0622-zAuthors Clifford E. Kashtan, University of Minnesota Medical School, University of Minnesota Children’s Hospital, Fairview Department of Pediatrics, Division of Pediatric Nephrology 420 Delaware Street SE, MMC 491 Minneapolis MN 55455 USA Journal Pediatric NephrologyOnline ISSN 1432-198XPrint ISSN 0931-041X (Source: Pediatric Nephrology)

Comparison of reflection contrast microscopy and electron microscopy on the histopathological diagnosis of various kidney diseases

Microscopy Research and Technique — Thu, 13 Sep 2007 04:00:00 +0100

Our aim in this study was to compare reflection contrast microscopy (RCM) with transmission electron microscopy (TEM) to understand whether RCM could be used in the histopathological diagnosis of various kidney diseases as a less expensive and an easier alternative to TEM. The diagnoses of kidney pathologic lesions included Alport syndrome, thin membrane disease, Ig A nephropathy. RCM is a form of light microscope that works in the reflected mode, suitable to observe ultrathin (50-100 nm) plastic sections that is also used in TEM. Our findings showed that RCM showed similar results compared with TEM on these lesions described earlier. Microsc. Res. Tech., 2007. © 2007 Wiley-Liss, Inc. (Source: Microscopy Research and Technique)

Autoepitopes and alloepitopes of type IV collagen: role in the molecular pathogenesis of anti-GBM antibody glomerulonephritis.

Nephron Experimental Nephrology — Thu, 06 Sep 2007 01:24:35 +0100

Authors: Borza DB Anti-glomerular basement membrane (anti-GBM) antibodies elicited by autoimmune or alloimmune mechanisms are associated with aggressive forms of rapid progressive glomerulonephritis. Pathogenic anti-GBM autoantibodies and alloantibodies target the noncollagenous (NC1) domains of the alpha3alpha4alpha5(IV) collagen, a major GBM component. In autoimmune anti-GBM glomerulonephritis, a breakdown of immune self-tolerance leads to the activation of autoreactive B and T cells recognizing epitopes within the alpha3NC1 subunit. In the GBM, the conformational epitopes targeted by anti-GBM autoantibodies are structurally sequestered within the alpha3alpha4alpha5NC1 hexamer complex formed upon assembly of collagen IV chains into trimeric molecules and networks. Autoantibodies sele...

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Alterations of type IV collagen alpha chains in patients with chronic acquired glomerulopathies: mRNA levels, protein expression and urinary loss.

American Journal of Nephrology — Thu, 06 Sep 2007 01:18:33 +0100

CONCLUSION: Patients with chronic acquired glomerulopathies show important alterations in the col(IV)alpha chain network mimicking some molecular features of the X-linked Alport's syndrome. Further studies are needed to show whether urinary levels of the col(IV)alpha chains may be used as markers for monitoring renal injury. PMID: 17308374 [PubMed - indexed for MEDLINE] (Source: American Journal of Nephrology)

A Novel Mutation of COL4A3 Presents a Different Contribution to Alport Syndrome and Thin Basement Membrane Nephropathy.

American Journal of Nephrology — Fri, 24 Aug 2007 04:00:00 +0100

Conclusion: The novel mutation (3725G>A, G1242D) of COL4A3 was the underlying pathogenic role in the homozygous form in ARAS and in the heterozygous form in TBMN within an identical family. The result provided a potentially useful clue for the functional investigation of COL4A3 in these two hereditary glomerular disorders. Copyright (c) 2007 S. Karger AG, Basel. PMID: 17726307 [PubMed - as supplied by publisher] (Source: American Journal of Nephrology)

Genetic Testing for X-Linked Alport Syndrome by Direct Sequencing of COL4A5 cDNA From Hair Root RNA Samples.

American Journal of Kidney Diseases — Wed, 01 Aug 2007 00:14:55 +0100

CONCLUSIONS: A more reliable linkage analysis and a simple, fast, and efficient mutation screening are now available for the genetic testing of patients with XLAS. PMID: 17660027 [PubMed - in process] (Source: American Journal of Kidney Diseases)

Alport Syndrome and Thin Basement Membrane Nephropathy

Nephron Clinical Practice — Sun, 17 Jun 2007 05:47:12 +0100

Nephron Clin Pract 2007;106:c82-c88 (DOI:10.1159/000101802) (Source: Nephron Clinical Practice)