FBXO11 variants are associated with intellectual disability and variable clinical manifestation in Chinese affected individuals
In this study, 12 intellectual disability individuals from 5 Chinese ID families were collected, and whole exome sequencing (WES), sanger sequencing, and RNA sequencing (RNA-seq) were conducted. Almost all the affected individuals presented with mild to severe intellectual disability (12/12), global developmental delay (10/12), speech and language development delay (8/12) associated with a range of alternate features including increased body weight (7/12), short stature (6/12), seizures (3/12), reduced visual acuity (4/12), hypotonia (1/12), and auditory hallucinations and hallucinations (1/12). Distinguishingly, malformat...
Source: Journal of Human Genetics - May 13, 2024 Category: Genetics & Stem Cells Source Type: research
A novel pathogenic mitochondrial DNA variant m.4344T & gt;C in tRNAGln causes developmental delay
In this study, we identified a novel variant m.4344T>C in mitochondrial tRNAGln from a patient with developmental delay. The mutant loads of m.4344T>C were 95% and 89% in the patient ’s blood and oral epithelial cells, respectively. Multialignment analysis showed high evolutionary conservation of this nucleotide. TrRosettaRNA predicted that m.4344T>C variant would introduce an additional hydrogen bond and alter the conformation of the T-loop. The transmitochondrial cybrid-based study demonstrated that m.4344T>C variant impaired the steady-state level of mitochondrial tRNAGln and decreased the contents of mito...
Source: Journal of Human Genetics - May 10, 2024 Category: Genetics & Stem Cells Source Type: research
Fundamentals for predicting transcriptional regulations from DNA sequence patterns
AbstractCell-type-specific regulatory elements, cataloged through extensive experiments and bioinformatics in large-scale consortiums, have enabled enrichment analyses of genetic associations that primarily utilize positional information of the regulatory elements. These analyses have identified cell types and pathways genetically associated with human complex traits. However, our understanding of detailed allelic effects on these elements ’ activities and on-off states remains incomplete, hampering the interpretation of human genetic study results. This review introduces machine learning methods to learn sequence-depend...
Source: Journal of Human Genetics - May 10, 2024 Category: Genetics & Stem Cells Source Type: research
Exploring the relationship between admixture and genetic susceptibility to attention deficit hyperactivity disorder in two Latin American cohorts
This study explores the relationship between admixture and genetic associations for ADHD in Colombian and Mexican cohorts. Some 546 participants in two groups, ADHD and Control, were genotyped with Infinium PsychArray ®. Global ancestry levels were estimated using overall admixture proportions and principal component analysis, while local ancestry was determined using a method to estimate ancestral components along the genome. Genome-wide association analysis (GWAS) was conducted to identify significant associat ions. Differences between Colombia and Mexico were evaluated using appropriate statistical tests. 354 Single-nu...
Source: Journal of Human Genetics - May 7, 2024 Category: Genetics & Stem Cells Source Type: research
Prevalence of FSH-R Asn680Ser and Ala307Thr receptor polymorphism and their correlation with ART outcomes among infertile Indian-Asian women-a prospective cohort study
AbstractThe present prospective cohort study evaluated the prevalence of FSH-R receptor Asn680Ser and Ala307Thr among infertile Indian women and the correlation of these polymorphisms with ART outcomes. Total 804 infertile and 209 fertile controls were enrolled for FSH-R analysis. Correlation of different genotypes with ovarian reserve markers, IVF parameters, and cumulative live birth rates (CLBR) was done among women undergoing IVF. In fertile controls, at 680 position GG (Ser/Ser) was the most common genotype; but among infertile women, all the genotypes were equally distributed. There was no significant difference in o...
Source: Journal of Human Genetics - April 25, 2024 Category: Genetics & Stem Cells Source Type: research
Mediation role of DNA methylation in association between handgrip strength and cognitive function in monozygotic twins
AbstractHandgrip strength is a crucial indicator to monitor the change of cognitive function over time, but its mechanism still needs to be further explored. We sampled 59 monozygotic twin pairs to explore the potential mediating effect of DNA methylation (DNAm) on the association between handgrip strength and cognitive function. The initial step was the implementation of an epigenome-wide association analysis (EWAS) in the study participants, with the aim of identifying DNAm variations that are associated with handgrip strength. Following that, we conducted an assessment of the mediated effect of DNAm by the use of mediat...
Source: Journal of Human Genetics - April 23, 2024 Category: Genetics & Stem Cells Source Type: research
Exploring inheritance, and clinical penetrance of distal Xq28 duplication syndrome: insights from 47 new unpublished cases
ConclusionOur study provides key insights into distal Xq28 duplication. Most prenatal tests showed no major fetal ultrasound issues. Maternal inheritance was common, with unaffected mothers. In the postnatal group, a balanced gender distribution was observed. Among male family members, two fathers had ADHD, one was healthy, and one brother had mild symptoms, indicating partial penetrance in males. (Source: Journal of Human Genetics)
Source: Journal of Human Genetics - April 18, 2024 Category: Genetics & Stem Cells Source Type: research
Role of TOE1 variants at the nuclear localization motif in pontocerebellar hypoplasia 7
AbstractBiallelicTOE1 variants can cause pontocerebellar hypoplasia type 7 (PCH7), a condition characterized by pontocerebellar hypoplasia with genital abnormality. TOE1 is a 3 ’-exonuclese for 3’-end maturation in small nuclear RNA.TOE1 pathogenic variants have been reported at the DEDD catalytic domain and zinc finger motif. Here, we describe a PCH7 patient with novel compound heterozygousTOE1 variants and a detailed clinical course. The patient was a 3-year-old female and showed developmental delay without cerebellar ataxic behavior. Head MRI revealed delayed myelination without pontocerebellar hypoplasia at 9 month...
Source: Journal of Human Genetics - April 11, 2024 Category: Genetics & Stem Cells Source Type: research
Heritability of complex traits in sub-populations experiencing bottlenecks and growth
AbstractPopulations that have experienced a bottleneck are regularly used in Genome Wide Association Studies (GWAS) to investigate variants associated with complex traits. It is generally understood that these isolated sub-populations may experience high frequency of otherwise rare variants with large effect size, and therefore provide a unique opportunity to study said trait. However, the demographic history of the population under investigation affects all SNPs that determine the complex trait genome-wide, changing its heritability and genetic architecture. We use a simulation based approach to identify the impact of the...
Source: Journal of Human Genetics - April 8, 2024 Category: Genetics & Stem Cells Source Type: research
Long-term course of a case with a novel homozygous kyphoscoliosis peptidase variant
AbstractWe herein report a case with a novel homozygous variant in thekyphoscoliosis peptidase (KY) gene. A 58-year-old Japanese female was referred to our hospital with a gait disturbance that gradually worsened after the age of 50. She had bilateral equinus foot deformity since early childhood. Neurological examination revealed moderate weakness of the neck, trunk, femoral, and brachial muscles, mild respiratory failure, and areflexia. Whole-exome sequencing revealed a novel homozygous frameshift variant of theKY gene, NM_178554.6:c.824del p.(Glu275Glyfs*53). Our case demonstrated thatKY-associated neuromuscular disease ...
Source: Journal of Human Genetics - April 8, 2024 Category: Genetics & Stem Cells Source Type: research
Identification of a novel LFNG variant in a Chinese fetus with spondylocostal dysostosis and a systematic review
This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases withLFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon ofLFNG. The variant was predicted to cause loss of fun...
Source: Journal of Human Genetics - April 2, 2024 Category: Genetics & Stem Cells Source Type: research
Correction: Genetic etiology of truncus arteriosus excluding 22q11.2 deletion syndrome and identification of c.1617del, a prevalent variant in TMEM260, in the Japanese population
(Source: Journal of Human Genetics)
Source: Journal of Human Genetics - March 29, 2024 Category: Genetics & Stem Cells Source Type: research
A mediation analysis framework based on variance component to remove genetic confounding effect
AbstractIdentification of pleiotropy at the single nucleotide polymorphism (SNP) level provides valuable insights into shared genetic signals among phenotypes. One approach to study these signals is through mediation analysis, which dissects the total effect of a SNP on the outcome into a direct effect and an indirect effect through a mediator. However, estimated effects from mediation analysis can be confounded by the genetic correlation between phenotypes, leading to inaccurate results. To address this confounding effect in the context of genetic mediation analysis, we propose a restricted-maximum-likelihood (REML)-based...
Source: Journal of Human Genetics - March 25, 2024 Category: Genetics & Stem Cells Source Type: research
Visit to visit transition in TXNIP gene methylation and the risk of type 2 diabetes mellitus: a nested case-control study
This study included 263 incident cases of T2DM and 263 matched non-T2DM participants. According to the methylation levels of five loci (CpG1 –5; chr1:145441102-145442001) on theTXNIP gene, the participants were classified into four transition groups: maintained low, low to high, high to low, and maintained high methylation levels. Compared with individuals whose methylation level of CpG2 –5 at theTXNIP gene was maintained low, individuals with maintained high methylation levels showed a 61 –87% reduction in T2DM risk (66% for CpG2 [OR: 0.34, 95% CI: 0.14, 0.80]; 77% for CpG3 [OR: 0.23, 95% CI: 0.07, 0.78]; 87% for Cp...
Source: Journal of Human Genetics - March 25, 2024 Category: Genetics & Stem Cells Source Type: research
Correction: The frequency and pathogenicity of BRCA1 and BRCA2 variants in the general Japanese population
(Source: Journal of Human Genetics)
Source: Journal of Human Genetics - March 14, 2024 Category: Genetics & Stem Cells Source Type: research
