中国智障家庭致LESKRES的一种新型AGO2变异的鉴定

IF 2.8 3区 生物学 Q2 GENETICS & HEREDITY
Frontiers in Genetics Pub Date : 2025-06-12 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1598462
Shufa Yang, Wei Song, Yousheng Yan
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引用次数: 0

摘要

背景:Lessel-Kreienkamp综合征(LESKRES, MIM #619149)是一种常染色体显性遗传疾病,由AGO2 (MIM*606229)变异引起,主要导致神经发育症状。目的:探讨一个智力障碍家庭的遗传病因。方法:采用全外显子组测序(full -exome sequencing, WES)初步鉴定家族中导致智力残疾的致病变异,并采用Sanger测序进行确认。收集完整的家族信息,并进行Sanger测序以确认变异与智力残疾的共分离,从而确定新变异的致病性。用计算机方法对新变异的致病性进行了评价。结果:4例智力障碍患者均携带新型AGO2 (NM_012154.5): C . 2149t >C (p.Cys717Arg)变异,其余患者未携带。根据ACMG指南,这种新变异被归类为可能致病。这种新变异发生在AGO2的保守位置,预计会影响AGO2蛋白的三维结构。结论:本研究首次在中国人群中鉴定出一种新的导致LESKRES的AGO2变异。我们的发现扩大了导致LESKRES的AGO2变异谱,并强调了WES在诊断智力残疾遗传原因方面的价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of a novel AGO2 variant causing LESKRES in a Chinese family with intellectual disability.

Background: Lessel-Kreienkamp syndrome (LESKRES, MIM #619149), an autosomal dominant genetic disorder caused by variants in AGO2 (MIM*606229), primarily leads to neurodevelopmental symptoms.

Objective: This study aims to investigate the genetic etiology of a family with intellectual disability.

Methods: Whole-exome sequencing (WES) was used to initially identify the pathogenic variants responsible for the intellectual disability in the family, and Sanger sequencing was employed for confirmation. Complete family information was collected, and Sanger sequencing was performed to confirm the co-segregation of the variant with the intellectual disability, thereby determining the pathogenicity of the novel variant. The pathogenicity of the novel variant was evaluated using in silico methods.

Results: All four intellectual disability individuals carried the novel AGO2 (NM_012154.5): c.2149T>C (p.Cys717Arg) variant, while the other individuals did not. According to ACMG guidelines, this novel variant is classified as likely pathogenic. The novel variant occurs at a conserved position in AGO2 and is predicted to affect the 3D structure of the AGO2 protein.

Conclusion: This study identifies a novel AGO2 variant causing LESKRES in the Chinese population for the first time. Our findings expand the variants spectrum of AGO2 leading to LESKRES and highlight the value of WES in diagnosing genetic causes of intellectual disabilities.

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来源期刊
Frontiers in Genetics
Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
5.50
自引率
8.10%
发文量
3491
审稿时长
14 weeks
期刊介绍: Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.
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