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Exploring inheritance, and clinical penetrance of distal Xq28 duplication syndrome: insights from 47 new unpublished cases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
Expanding the genetic and phenotypic spectrum of TRAPPC9 and MID2-related neurodevelopmental disabilities: report of two novel mutations, 3D-modelling, and molecular docking studies
AbstractIntellectual disabilities (ID) and autism spectrum disorders (ASD) have a variety of etiologies, including environmental and genetic factors. Our study reports a psychiatric clinical investigation and a molecular analysis using whole exome sequencing (WES) of two siblings with ID and ASD from a consanguineous family. Bioinformatic prediction and molecular docking analysis were also carried out. The two patients were diagnosed with profound intellectual disability, brain malformations such as cortical atrophy, acquired microcephaly, and autism level III. The neurological and neuropsychiatric examination revealed tha...
Source: Journal of Human Genetics - March 11, 2024 Category: Genetics & Stem Cells Source Type: research
A bird ’s eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases
AbstractPhenotypic and genotypic heterogeneity in congenital ocular diseases, especially in anterior segment dysgenesis (ASD), have created challenges for proper diagnosis and classification of diseases. Over the last decade, genomic research has indeed boosted our understanding in the molecular basis of ASD and genes associated with both autosomal dominant and recessive patterns of inheritance have been described with a wide range of expressivity. Here we describe the molecular characterization of a cohort of 162 patients displaying isolated or syndromic congenital ocular dysgenesis. Samples were analyzed with diverse tec...
Source: Journal of Human Genetics - March 8, 2024 Category: Genetics & Stem Cells Source Type: research
New insights into the clinical and molecular spectrum of the MADD-related neurodevelopmental disorder
AbstractBiallelic pathogenic variants inMADD lead to a very rare neurodevelopmental disorder which is phenotypically pleiotropic grossly ranging from severe neonatal hypotonia, failure to thrive, multiple organ dysfunction, and early lethality to a similar but milder phenotype with better survival. Here, we report 5 patients from 3 unrelated Egyptian families in whom 4 patients showed the severe end of the spectrum displaying neonatal respiratory distress, hypotonia and chronic diarrhea while one patient presented with the mild form displaying moderate intellectual disability and myopathy. In addition, we observed distal a...
Source: Journal of Human Genetics - March 8, 2024 Category: Genetics & Stem Cells Source Type: research
Correction: The c.1617del variant of TMEM260 is identified as the most frequent single gene determinant for Japanese patients with a specific type of congenital heart disease
(Source: Journal of Human Genetics)
Source: Journal of Human Genetics - March 8, 2024 Category: Genetics & Stem Cells Source Type: research
