Unveiling Hidden Genetic Architectures: Molecular Diagnostic Yield of Whole Exome Sequencing in 50 Children With Autism Spectrum Disorder Negative for Copy Number Variations.

IF 1.4 4区生物学 Q4 GENETICS & HEREDITY

Genetics research Pub Date : 2025-07-03 eCollection Date: 2025-01-01 DOI:10.1155/genr/5724454

Zhiwei Wang, Yali Zhao, Shuting Yang, Yongan Wang, Leilei Wang

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引用次数: 0

Abstract

Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental conditions with complex genetic etiologies. Recent advances in whole exome sequencing (WES) have enabled comprehensive detection of clinically relevant variants, particularly single-nucleotide variations (SNVs) and InDels, in ASD genetic diagnostics. Here, we performed WES on 50 Chinese children with ASD who tested negative for copy number variants (CNVs). The analysis achieved a diagnostic yield of 10% (5/50 cases). All SNVs and InDels were loss-of-function (LOF) and were slightly more frequent among females (male vs. female: 9.3% vs. 14.3%). A total of five causative genes (PRODH9, PTEN, DEPDC5, SATB2, and CYFIP1) were identified in this study. Variants in ASD-associated genes (CHD8, FOXP1, and SHANK1) and genes linked to other neurodevelopmental disorders (CDH15, GATAD2B, and SHROOM4) were also detected. Despite the small sample size, our findings contribute partially to the dataset on the phenotype and genetic etiology of ASD and underscore WES as a critical tool for elucidating genetic etiologies in CNV-negative ASD cohorts.

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揭示隐藏的遗传结构：50例拷贝数变异阴性的自闭症谱系障碍儿童的全外显子组测序的分子诊断产量。

自闭症谱系障碍（ASDs）是具有复杂遗传病因的异质神经发育疾病。全外显子组测序（WES）的最新进展使得在ASD遗传诊断中能够全面检测临床相关变异，特别是单核苷酸变异（snv）和InDels。在这里，我们对50名拷贝数变异（CNVs）检测为阴性的中国ASD儿童进行了WES检测。该分析的诊断率为10%（5/50例）。所有snv和InDels均为功能丧失（LOF），在女性中发生率略高（男性vs女性：9.3% vs 14.3%）。本研究共鉴定出5个致病基因（PRODH9、PTEN、DEPDC5、SATB2、CYFIP1）。asd相关基因（CHD8、FOXP1和SHANK1）和其他神经发育障碍相关基因（CDH15、GATAD2B和SHROOM4）的变异也被检测到。尽管样本量小，但我们的研究结果在一定程度上有助于建立ASD的表型和遗传病因数据集，并强调WES是阐明cnv阴性ASD队列遗传病因的关键工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genetics research 生物-遗传学

自引率

6.70%

发文量

审稿时长

>12 weeks

期刊介绍： Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.