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Comprehensive clinical and genetic profiling of Vietnamese pediatric hearing loss: a multi-region exome sequencing study.

Congenital hearing loss (HL) in the Vietnamese population remains understudied despite its genetic diversity, limiting our understanding of its genetic etiology and hindering the development of effective, population-specific diagnostic strategies. In this descriptive cross-sectional whole-exome sequencing study, we enrolled 150 children with congenital non-syndromic HL (NSHL) from hospitals and hearing centers across Northern, Central, and Southern Vietnam to describe the genetic landscape of HL and provide new insights into rare and HL-associated variants. Clinical variant annotation was perf…

Somatic likelihood tiering: an interpretable post-calling triage protocol for tumor-only whole-exome variant review.

Tumor-only whole-exome sequencing (WES) is used when matched normal tissue is unavailable, but one sample can produce thousands of variants. Somatic likelihood tiering (SLT) is an interpretable post-calling protocol that ranks Mutect2 calls into four review-priority tiers using population-frequency, germline-quality, cancer-knowledge, PureCN posterior, and clonal-hematopoiesis evidence. Layer 2 distinguishes common, rare-callable, and unevaluable gnomAD states; missing or unmatchable gnomAD evidence is not positive rarity evidence. On the SEQC2 HCC1395 benchmark, the callability-aware SLT-A ro…

Identification of molecular biomarkers associated with non-small-cell lung carcinoma (NSCLC) using whole-exome sequencing.

ObjectivesSignificant progress has been made in the treatment of patients with pulmonary adenocarcinoma (ADCA) based on molecular profiling. However, no such molecular target exists for squamous cell carcinoma (SQCC). An exome sequence may provide new markers for personalized medicine for lung cancer patients of all subtypes. The current study aims to discover new genetic markers that can be used as universal biomarkers for non-small cell lung cancer (NSCLC).MethodsWES of 19 advanced NSCLC patients (10 ADCA and 9 SQCC) was performed using Illumina HiSeq 2000. Variant calling was performed usin…

Whole exome sequencing reveals an FCGBP variant associated with spontaneous intraabdominal hemorrhage in severe acute pancreatitis.

This study investigated the genetic basis of spontaneous intraabdominal hemorrhage (SIH) in severe acute pancreatitis (SAP) to facilitate the development of more effective treatments for this life-threatening complication. A four-phase study was conducted with a large cohort of acute pancreatitis (AP) patients (n = 600). In the first phase, whole-exome sequencing identified a specific exonic variant (rs1326680184) in the human Fc gamma binding protein (FCGBP) gene consistently associated with SIH. The second phase employed serum ELISA tests, revealing that this variant altered FCGBP protein le…

Whole exome sequence reveals genetic profiles of primary cardiomyopathy and genotype-phenotype association in Chinese population.

BACKGROUND: Primary cardiomyopathies are major causes of heart failure, placing a substantial burden on both individuals and society. Revealing its genetic profiles can lead to a better understanding of the mechanism and is critical for disease prevention and treatment. METHOD: Primary cardiomyopathy patients were enrolled and whole exome sequence was conducted to analyze their genetic profiles. Retrospective clinical information extraction and analysis of sequence data were implemented. RESULTS: A total of 77 primary cardiomyopathy patients were enrolled, comprising 65 patients with dilated…

Exome sequencing reveals new insights into the germline landscape of inflammatory breast cancer among Tunisian patients.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, characterized by distinct clinicopathological features and a relatively high frequency in North African countries. While several studies have explored the genetic basis of breast cancer, limited research has looked into the specific genetic features of this aggressive form. This study aims to investigate the genetic factors associated with IBC in North Africa, particularly among Tunisian patients. METHODS: Whole exome sequencing was performed for 13 patients with IBC. Clinicopathological data have bee…

Putative multiple myeloma susceptibility genes identified by exome sequencing of 347 familial and early-onset cases.

Multiple myeloma (MM) is the second most common blood malignancy, with several lines of evidence supporting an inherited genetic component. Here, we sequenced 177 affected individuals from 128 families, and 170 early-onset MM cases diagnosed before 55 years of age. Samples were identified and collected through nationwide efforts in France, Sweden, and Greece. We focused on rare germline protein truncating and likely deleterious missense variants in genes harboring variants in at least two families showing variant-disease segregation, and in additional index (≥2) and/or early-onset (≥2) cases.

Whole-exome sequencing identifies TRIM72 as a candidate gene for autosomal recessive limb-girdle muscular dystrophy.

BACKGROUND: Limb-girdle muscular dystrophies (LGMDs) constitute a genetically diverse group of disorders characterized by progressive proximal muscle weakness and atrophy. Despite advances in genetic diagnostics, numerous cases remain unresolved due to extensive genetic heterogeneity, emphasizing the necessity for continued identification of novel pathogenic variants. RESULTS: Using whole-exome sequencing (WES) in a Saudi family affected by autosomal recessive LGMD, we identified a novel homozygous frameshift mutation (c.891delT; p.Ala298ArgfsTer64) in the TRIM72 (MG53) gene, which we propose…

Exome Sequencing Reveals Novel Variants in Genetic Skeletal Disorders: Insights From a Cohort in Southwest Iran.

Genetic skeletal disorders (GSDs) comprise a diverse group of disorders that affect bone development and homeostasis. In some areas of Iran, GSD occurs more frequently than in other places for still unknown reasons. The aim of this study was to characterize the genetic landscape of GSDs in a cohort from southwestern Iran using Exome sequencing (ES), with a focus on identifying pathogenic and likely pathogenic variants. Osteogenesis Imperfecta (OI) was the most prevalent disorder, with an unexpectedly high frequency of autosomal recessive subtypes, likely due to a high consanguinity rate (61.3%…

Identifying the germline variation spectrum and predisposition genes in Chinese ovarian cancer using whole exome sequencing.

BACKGROUND: Next-generation sequencing (NGS) allows for the simultaneous sequencing of multiple cancer predisposition genes. We assessed the frequency and spectrum of germline variations in individuals with ovarian cancer (OC), using whole exome sequencing (WES). METHODS: A total of 92 patients with OC, with or without a family history of cancer, were consecutively recruited between May 2020 and September 2023. Germline DNA was sequenced using WES. RESULTS: Among the 12 canonical OC predisposition genes recommended by the National Comprehensive Cancer Network (NCCN) guidelines, 26 patients (…

Сексуальная последовательность показывает низкочастотные и редкие варианты воздействия на подверженность множественным склерозам в турецких семьях.

Множественный склероз (MS) характеризуется как болезнь центральной нервной системы с иммунной помощью, которая характеризуется хроническим воспалением, обезвоживанием и прогрессивным нейродегенерацией. В этом исследовании мы проанализировали вклад низкочастотных и редких генетических вариантов в подверженность MS в рамках одной из крупнейших на сегодняшний день семейных групп MS, в состав которых входят 215 человек из 59 турецких семей с множественными MS. На всех образцах, включая затронутых и не затронутых членов, была проведена целая последовательность экзотических операций, за которой посл

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is characterized as an immune-mediated central nervous system disease marked by chronic inflammation, demyelination, … y-based MS cohorts to date, comprising 215 individuals from 59 Turkish multiplex MS families. Whole exome sequencing was conducted on all samples including affected and unaffected members, followed by investigation of the effect of well-established human leukocyte antigen loci for MS on the elevated MS risk observed in our families. Subsequently, a gene …

Whole-exome sequencing and Drosophila modelling reveal mutated genes and pathways contributing to human ovarian failure.

BACKGROUND: Ovarian failure (OF) is a multifactorial, complex disease presented by up to 1% of women under 40 years of age. Despite 90% of patients being diagnosed with idiopathic OF, the underlying molecular mechanisms remain unknown, making it difficult to personalize treatments for these patients in the clinical setting. Studying the presence and/or accumulation of SNVs at the gene/pathway levels will help describe novel genes and characterize disrupted biological pathways linked with ovarian failure. METHODS: Ad-hoc case-control SNV screening conducted from 2020 to 2023 of 150 VCF files W

Clinical exome sequencing uncovers genetic disorders in neonates with suspected hypoxic-ischemic encephalopathy: A retrospective analysis.

Hypoxic-ischemic encephalopathy (HIE) occurs in up to 7 out of 1000 births and accounts for almost a quarter of neonatal deaths worldwide. Despite the name, many newborns with HIE have little evidence of perinatal hypoxia. We hypothesized that some infants with HIE have genetic disorders that resemble encephalopathy. We reviewed genetic results for newborns with HIE undergoing exome or genome sequencing at a clinical laboratory (2014-2022). Neonates were included if they had a diagnosis of HIE and were delivered ≥35 weeks. Neonates were excluded for cardiopulmonary pathology resulting in hypox…

Genetic testing for fetal loss of heterozygosity using single nucleotide polymorphism array and whole-exome sequencing.

The study explored the clinical significance of fetal loss of heterozygosity (LOH) identified by single-nucleotide polymorphism array (SNP array). We retrospectively reviewed data from pregnant women who underwent invasive diagnostic procedures at prenatal diagnosis centers in southeastern China from December 2016 to December 2021. SNP array was performed by the Affymetrix CytoScan 750 K array platform. Fetuses with LOH were further identified by parental verification, MS-MLPA, and/or trio whole-exome sequencing (trio-WES). The genetic results, fetal clinical manifestations, and perinatal outc…

Pathogenic cryptic variants detectable through exome data reanalysis significantly increase the diagnostic yield in Joubert syndrome.

Joubert syndrome (JS) is a genetically heterogeneous neurodevelopmental ciliopathy. Despite exome sequencing (ES), several patients remain undiagnosed. This study aims to increase the diagnostic yield by uncovering cryptic variants through targeted ES reanalysis. We first focused on 26 patients in whom ES only disclosed heterozygous pathogenic coding variants in a JS gene. We reanalyzed raw ES data searching for copy number variants (CNVs) and intronic variants affecting splicing. We validated CNVs through real-time PCR or chromosomal microarray, and splicing variants through RT-PCR or minigen…

Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a food allergy primarily affecting infants, often leading to vomiting and … les from 41 patients with oral food challenge-proven FPIES were collected for a comprehensive whole exome sequencing association study. RESULTS: Notable genetic variants, including rs872786 (RBM8A), rs2241880 (ATG16L1) and rs2289477 (ATG16L1), were identified as significant findings in FPIES. A weighted SKAT model identified six other associated genes …

Clinical exome sequencing reveals a novel pathogenic variant in KIF12 underlying cholestasis with highly variable phenotypes.

Four affected individuals from a large consanguineous family were diagnosed with variable phenotypes of cholestasis based on their clinical laboratory and biopsy findings. Cholestasis is a condition when there is not enough bile flow between liver and small intestine. Two of the affected individuals (IV-1, IV-4) died of cholestatic liver at an early age, while the other two patients are alive with chronic liver disease. Clinical exome and Sanger sequencing identified a novel homozygous pathogenic variant (c.482-7_500del) in the patients.

Exome sequencing and functional analyses revealed CETN1 variants leads to impaired cell division and male fertility.

Human spermatogenesis requires an orchestrated expression of numerous genes in various germ cell subtypes. Therefore, the genetic landscape of male infertility is highly complex. Known genetic factors alone account for at least 15% of male infertility. However, ~40% of infertile men remain undiagnosed and are classified as idiopathic infertile men. We performed exome sequencing in 47 idiopathic infertile men (discovery cohort), followed by replication study (40 variants in 33 genes) in 844 infertile men and 709 controls using Sequenom MassARRAY® based genotyping. We report 17 variants in twelv…

Whole-Exome Sequencing Reveals Migraine-Associated Novel Functional Variants in Arab Ancestry Females: A Pilot Study.

Migraine, as the seventh most disabling neurological disease with 26.9% prevalence in Saudi females, lacks studies on identifying associated genes and pathways with migraines in the Arab population. This case control study aims to identify the migraine-associated novel genes and risk variants. More than 1900 Arab ancestry young female college students were screened: 103 fulfilled the ICHD-3 criteria for migraine and 20 cases confirmed in the neurology clinic were included for the study with age-matched healthy controls. DNA from blood samples were subjected to paired-end whole-exome sequencing…