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Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.

BACKGROUND: Childhood apraxia of speech (CAS) is a rare, severe, persistent pediatric motor speech disorder with associated deficits in sensorimotor, cognitive, language, learning and affective processes. Among other neurogenetic origins, CAS is the disorder segregating with a mutation in FOXP2 in a widely studied, multigenerational London family. We report the first whole-exome sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to 19 years, with well-characterized CAS. METHODS: As part of a larger study of children and youth with motor speech sound disorders, 32 par…

Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia.

The corpus callosum is the principal cerebral commissure connecting the right and left hemispheres. The development of the corpus callosum is under tight genetic control, as demonstrated by abnormalities in its development in more than 1,000 genetic syndromes. We recruited more than 25 families in which members affected with corpus callosum hypoplasia (CCH) lacked syndromic features and had consanguineous parents, suggesting recessive causes. Exome sequence analysis identified C12orf57 mutations at the initiator methionine codon in four different families. C12orf57 is ubiquitously expressed an…

Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations.

The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricula … c classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as …

Identification of Variants in Two Families With Congenital Cataract by Whole Exome Sequencing.

BACKGROUND: Congenital cataract (CC) is an ophthalmic disorder diagnosed at birth or during early infancy, characterized by severe visual impairment and potential blindness. This study aimed to evaluate the pathogenicity of two variants: GJA8 c.201C>G (p.Asp67Glu) and CRYBB2 c.325A>T (p.Ile109Phe). METHODS: The patient's lenses were examined using slit-lamp photography and B-ultrasound. Whole-exome sequencing (WES) and sanger sequencing were performed to identify the variants. Multiple sequence alignment was conducted using CLUSTALW to assess the evolutionary conservation of the affected resi…

First Detection of 1p36 Deletion by Whole-Exome Sequencing in a Tunisian Patient.

STUDY OBJECTIVE: We reported a rare case of 1p36 deletion syndrome diagnosed using whole-exome sequencing (WES) in a Tunisian neonate, and to highlight the utility of WES in detecting structural variants, particularly in resource-limited settings. METHODS: Clinical and genetic investigations were conducted on a female neonate presenting with a severe polymalformative syndrome. WES was performed to detect potential genetic abnormalities, followed by validation through fluorescence in situ hybridization (FISH). Variant annotation and classification were done in accordance with ACMG guidelines. …

Screening for genetic kidney diseases in a dialysis cohort via exome sequencing.

BACKGROUND: Monogenic causes are increasingly recognized in end-stage kidney disease (ESKD), but the real-world diagnostic efficacy of exome sequencing in unselected dialysis cohorts is still being defined. METHODS: We conducted a prospective study enrolling 317 adult ESKD patients from a single center in Taiyuan, China, regardless of presumed etiology. Whole-exome sequencing (WES) was performed on peripheral blood DNA. Variants were curated and classified per the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) 2015 and Association for Clinical…

From sample to clinical insight: a review of exome sequencing in disease diagnostics.

Exome sequencing (ES) has transformed genomic research and clinical diagnostics by enabling precise identification of disease-associated variants within protein-coding regions, which, while representing a minority of the genome, include many well-characterized pathogenic mutations. This review provides a comprehensive overview of ES methodology, data analysis pipelines, clinical relevance, and ethical considerations. We describe the ES workflow from DNA extraction and library preparation to target enrichment, sequencing to ES data analysis. We have also evaluated major capture technologies and…

Clinical utility of trio whole exome sequencing in fetuses with ultrasound anomalies.

INTRODUCTION: Ultrasound scanning anomalies in fetuses are a cause for concern and often necessitate further diagnostic procedures. This retrospective study evaluated the utility of trio whole exome sequencing (trio-WES) in the diagnosis of fetuses with ultrasound anomalies. METHODS: We included fetuses diagnosed with fetal ultrasound anomalies referred to the First Affiliated Hospital of Chongqing Medical University between November 2018 and July 2023. Fetal anomalies were classified into structural anomalies, dynamic anomalies, and soft markers. Karyotype analysis, chromosomal microarray an…

[Diagnostic value of whole exome sequencing in difficult and complicated pulmonary diseases].

Objective: To evaluate the diagnostic value of whole exome sequencing (WES) for difficult and complicated pulmonary diseases. Methods: A retrospective analysis was conducted on patients with difficult and complicated pulmonary diseases who underwent WES at Peaking Union Medical College Hospital from May 2021 to August 2024. Demographic information, clinical data, and WES results were collected and systematically analyzed. Results: A total of 24 patients were included, comprising 14 males (58.33%) and 10 females (41.67%). The median age of the patients was 28 years (range: 14-64 years). WES ide…

Exome sequencing for nonimmune hydrops fetalis and clinical utility of data reanalysis.

BACKGROUND: Nonimmune hydrops fetalis (NIHF) presents as life-threatening fluid collections in multiple fetal compartments and may be led by numerous etiologies. AIM: To establish the diagnostic yield of exome sequencing for single-gene disorders in unexplained NIHF and to evaluate the clinical utility of data reanalysis. METHODS: A series of 53 unexplained cases of NIHF were enrolled, including 39 cases met a strict definition of NIHF and 14 cases with increased nuchal translucency (NT) and/or cystic hygroma in combination with other fluid collections. Trio ES from fetal samples and parenta…

Экзомная последовательность не прикрывает генетические движущие силы множественного склероза в семье мультиплексов.

Фон: Множественный склероз (MS) представляет собой хроническое, аутоиммунное, многофакторное и сложное расстройство центральной нервной системы (CNS), затрагивающее более 2 миллионов человек во всем мире. Исследования ассоциации геномов (GWAS) объясняют лишь небольшую долю его высокой наследственности, подчеркивая необходимость альтернативных подходов к выявлению редких генетических вариантов, способствующих его этиологии. Для решения этой проблемы в многострадальной семье мы провели целую последовательность (WES). Методы: WES была осуществлена в семье с несколькими поколениями, состоящей из д

Совпадение в аннотации оригинала
Background: Multiple Sclerosis (MS) is a chronic, autoimmune, multifactorial, and complex disorder of the central nervous system (CNS), affe … identify rare genetic variants that contribute to its etiology. To address this, we performed whole-exome sequencing (WES) in a multi-affected family. Methods: WES was performed in a MS multigenerational family comprising two affected sisters, their two healthy brothers, and one affected son. Results: Bioinformatics analysis identified 47 co-segregating …

Utility of exome sequencing in primary spermatogenic disorders: From research to diagnostics.

BACKGROUND: Primary spermatogenic disorders represent a severe form of male infertility whereby sperm production is impaired due to testicular dysfunction, leading to reduced quality or quantity of spermatozoa. Gene-centered research has certainly demonstrated the importance of the genetic factor in the etiology of both poor sperm morphology or motility and reduced sperm count. In the last decade, next-generation sequencing has expanded the research to whole exome which has transformed our understanding of male infertility genetics, but uncertainty persists in its diagnostic yield, especially …

Application of Whole-Exome Sequencing in the Genetic Diagnosis of Prenatal Ultrasound Abnormalities.

Aims/Background Prenatal diagnosis is a crucial tool in reducing birth defects. Research indicates that whole-exome sequencing (WES) is particularly effective for detecting abnormalities associated with structural ultrasound findings. This study aimed to evaluate the utility of WES in the genetic diagnosis of prenatal ultrasound abnormalities. Methods A total of 50 pregnant women with prenatal ultrasound abnormalities, diagnosed at Rizhao People's Hospital between January 2023 and May 2024, were enrolled. Amniocytes, abortion tissues, and peripheral blood samples from the couples were collecte…

Prenatal exome sequencing for the morphologically normal fetus: Should we be doing it?

OBJECTIVE: We aimed to investigate the yield of prenatal exome sequencing (pES) in morphologically normal fetuses. METHOD: This retrospective study analyzed 254 families with morphologically normal fetuses who underwent prenatal trio exome sequencing based on parental request between September 2020 and October 2023. RESULTS: Overall, abnormal findings were detected in 8 families (3.1%, 8/254) by pES. Among these, 6 families (2.3%, 6/254) were found to have fetuses affected with monogenic disorders (2 autosomal recessive conditions and 4 autosomal dominant conditions), while 2 families (0.8%,…

Diagnostic Yield of Exome Sequencing in Early-Onset Hypertensive Nephropathy in Adults.

INTRODUCTION: Hypertensive nephrosclerosis (HN) ranks as one of the most frequent causes of chronic kidney disease (CKD), but its very existence has repeatedly been called into question, especially in young adults. Its diagnostic framework is established chiefly on non-specific clinical criteria, and its defining histopathological set of features is in fact shared by numerous other conditions. Genetic testing based on exome sequencing (ES) has emerged as a comprehensive tool to detect Mendelian diseases in timely fashion in nephrology, with a significant number of re-established diagnoses. The…

Advancing diagnosis and management of liver disease in adults through exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) is an effective tool for diagnosis in patients who remain undiagnosed despite a comprehensive clinical work-up. While WES is being used increasingly in pediatrics and oncology, it remains underutilized in non-oncological adult medicine, including in patients with liver disease, in part based on the faulty premise that adults are unlikely to harbor rare genetic variants with large effect size. Here, we aim to assess the burden of rare genetic variants underlying liver disease in adults at two major tertiary referral academic medical centers. METHODS: WE…

Fast and reliable detection of repeat expansions in spinocerebellar ataxia using exomes.

Usually, molecular diagnosis of spinocerebellar ataxia is based on a step-by-step approach with targeted sizing of four repeat expansions accounting for most dominant cases, then targeted sequencing of other genes. Nowadays, genome sequencing allows detection of most pathogenic variants in a single step. The ExpansionHunter tool can detect expansions in short-read genome sequencing data. Recent studies have shown that ExpansionHunter can also be used to identify repeat expansions in exome sequencing data. We tested ExpansionHunter on spinocerebellar ataxia exomes in a research context as a sec…

The new frontier: a case for whole exome sequencing with multiple fetal anomalies.

OBJECTIVES: Standard genetic testing can fail to identify an underlying genetic etiology in pregnancies affected by multiple fetal abnormalities. Recently, whole exome sequencing (WES) studies have shown promise in recognizing genetic diagnoses where standard genetic testing does not yield answers. CASE PRESENTATION: A 35-year-old G1P0 healthy female found at anatomy scan to have multiple fetal anomalies, including severe bilateral ventriculomegaly, renal pyelectasis, and short long bones. Karyotype and microarray were normal. Whole exome sequencing showed the fetus was compound heterozygous …

Whole-exome sequencing establishes a diagnosis of Alstrom syndrome: a case report.

BACKGROUND: Alstrom syndrome (ALMS) is a rare genetic disorder. ALMS is characterized by progressive bilateral sensorineural hearing impairment, cone-rod dystrophy, infantile-onset cardiomyopathy, hypertriglyceridemia, accelerated non-alcoholic fatty liver disease, renal dysfunction and insulin-resistant diabetes mellitus (DM). DM typically develop in childhood or adolescence. Dilated cardiomyopathy may arise in infancy. Clinical symptoms appear with great variability and severity. Several cases have been reported worldwide; however, diagnosis remains challenging. CASE DESCRIPTION: We report

Whole-exome Sequencing Analysis of a Japanese Patient With Hyperinsulinemia and Liver Dysfunction.

Hyperinsulinemia is often observed in obese subjects because of insulin resistance, but it may occur in nonobese subjects with unknown etiol … by liver biopsy. We suspected genetic abnormalities related to hyperinsulinemia. We performed whole-exome sequencing (WES) analyses and identified a heterozygous nonsense variant p.R924X in the insulin receptor (INSR) gene, a novel heterozygous missense variant p.V416M in the AKT1 gene, and a novel hemizygous missense variant p.R310Q in the PHKA2 gene, …