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
Combined exome and whole transcriptome sequencing identifies a de novo intronic SRCAP variant causing DEHMBA syndrome with severe sleep disorder
This study demonstrated the efficacy of a combined ES-WTS approach in solving undiagnosed cases. We also speculated that sleep respiratory disorder may be an underdiagnosed complication of DEHMBA syndrome. (Source: Journal of Human Genetics)
Source: Journal of Human Genetics - March 7, 2024 Category: Genetics & Stem Cells Source Type: research
Weighted burden analysis of rare coding variants in 470,000 exome-sequenced UK Biobank participants characterises effects on hyperlipidaemia risk
AbstractA previous study of 200,000 exome-sequenced UK Biobank participants investigating the association between rare coding variants and hyperlipidaemia had implicated four genes,LDLR,PCSK9,APOC3 andIFITM5, at exome-wide significance. In addition, a further 43 protein-coding genes were significant with an uncorrectedp value of<0.001. Exome sequence data has become available for a further 270,000 participants and weighted burden analysis to test for association with hyperlipidaemia was carried out in this sample for the 47 genes highlighted by the previous study. There was no evidence to implicateIFITM5 butLDLR,PCSK9,A...
Source: Journal of Human Genetics - March 7, 2024 Category: Genetics & Stem Cells Source Type: research
Correction: Genetic association and functional validation of ZFP36L2 in non-syndromic orofacial cleft subtypes
(Source: Journal of Human Genetics)
Source: Journal of Human Genetics - March 5, 2024 Category: Genetics & Stem Cells Source Type: research
Potential drug targets for gastroesophageal reflux disease and Barrett ’s esophagus identified through Mendelian randomization analysis
This study aimed to find new drug targets for GERD and Barrett ’s esophagus (BE). We obtained genetic instruments for GERD, BE, and 2004 plasma proteins from recently published genome-wide association studies (GWAS), and Mendelian randomization (MR) was employed to explore potential drug targets. We further winnowed down MR-prioritized proteins through replic ation, reverse causality testing, colocalization analysis, phenotype scanning, and Phenome-wide MR. Furthermore, we constructed a protein-protein interaction network, unveiling potential associations among candidate proteins. Simultaneously, we acquired mRNA express...
Source: Journal of Human Genetics - March 1, 2024 Category: Genetics & Stem Cells Source Type: research
Advances in AI and machine learning for predictive medicine
AbstractThe field of omics, driven by advances in high-throughput sequencing, faces a data explosion. This abundance of data offers unprecedented opportunities for predictive modeling in precision medicine, but also presents formidable challenges in data analysis and interpretation. Traditional machine learning (ML) techniques have been partly successful in generating predictive models for omics analysis but exhibit limitations in handling potential relationships within the data for more accurate prediction. This review explores a revolutionary shift in predictive modeling through the application of deep learning (DL), spe...
Source: Journal of Human Genetics - February 29, 2024 Category: Genetics & Stem Cells Source Type: research
Dyssegmental dysplasia Rolland –Desbuquois type is caused by pathogenic variants in HSPG2 - a founder haplotype shared in five patients
AbstractDyssegmental dysplasia (DD) is a severe skeletal dysplasia comprised of two subtypes: lethal Silverman –Handmaker type (DDSH) and nonlethal Rolland–Desbuquois type (DDRD). DDSH is caused by biallelic pathogenic variants inHSPG2 encoding perlecan, whereas the genetic cause of DDRD remains undetermined. Schwartz –Jampel syndrome (SJS) is also caused by biallelic pathogenic variants inHSPG2 and is an allelic disorder of DDSH. In SJS and DDSH, 44 and 8 pathogenic variants have been reported inHSPG2, respectively. Here, we report that five patients with DDRD carried four pathogenic variants inHSPG2: c.9970 G ...
Source: Journal of Human Genetics - February 29, 2024 Category: Genetics & Stem Cells Source Type: research
The frequency and pathogenicity of BRCA1 and BRCA2 variants in the general Japanese population
AbstractHereditary breast and ovarian cancer syndrome (HBOC) resulting from pathogenic variants ofBRCA1 orBRCA2 is the most common and well-documented hereditary tumor. Although founder variants have been identified in population-based surveys in various countries, the types of variants are not uniform across races and regions. Recently, the Tohoku Medical Megabank Organization (ToMMo) released whole-genome sequence data including approximately 54,000 individuals from the general population of the Tohoku area in Japan. We analyzed these data and comprehensively identified the prevalence ofBRCA1/2 pathogenic and truncating ...
Source: Journal of Human Genetics - February 27, 2024 Category: Genetics & Stem Cells Source Type: research
Identifying the genetic associations among the psoriasis patients in eastern India
AbstractPsoriasis is a multifactorial genetic disorder manifested by hyperproliferation and abnormal differentiation of epidermal keratinocytes, along with the infiltration of inflammatory cells into the skin. Although ~80 genetic susceptibility variants were reported in psoriasis, many loci showed population-specific associations, warranting the need for more population-specific association studies in psoriasis. We determined the association of forty single nucleotide polymorphisms (SNPs) among 2136 psoriasis patients and normal individuals from eastern India. We investigated the expression of corresponding genes and eval...
Source: Journal of Human Genetics - February 27, 2024 Category: Genetics & Stem Cells Source Type: research
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
We reported that the pathogenic variant c.1617del ofTMEM260, which encodes a transmembrane protein, is highly associated with CHD, specifically persistent truncus arteriosus (PTA), the most severe cardiac outflow tract (OFT) defect. Using whole-exome sequencing, the c.1617del variant was identified in two siblings with PTA in a Japanese family and in three of the 26 DNAs obtained from Japanese individuals with PTA. The c.1617del ofTMEM260 has been found only in East Asians, especially Japanese and Korean populations, and the frequency of this variant in PTA is estimated to be next to that of the 22q11.2 deletion, the most ...
Source: Journal of Human Genetics - February 26, 2024 Category: Genetics & Stem Cells Source Type: research
Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review
In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in theCAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on humanCAPZA2 defects, documenting the fourth unambiguously diagnosed case. Fu...
Source: Journal of Human Genetics - February 19, 2024 Category: Genetics & Stem Cells Source Type: research
Leigh syndrome with developmental regression and ataxia due to a novel splicing variant in the PMPCB gene
We report the first splice site variant in thePMPCB gene in a 39-year old individual who experienced developmental regression and ataxia following otitis media in childhood. A minigene assay confirms this variant results in aberrant splicing and skipping of exon 12. (Source: Journal of Human Genetics)
Source: Journal of Human Genetics - February 19, 2024 Category: Genetics & Stem Cells Source Type: research
