{"title":"中国智障家庭致LESKRES的一种新型AGO2变异的鉴定","authors":"Shufa Yang, Wei Song, Yousheng Yan","doi":"10.3389/fgene.2025.1598462","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lessel-Kreienkamp syndrome (LESKRES, MIM #619149), an autosomal dominant genetic disorder caused by variants in <i>AGO2</i> (MIM*606229), primarily leads to neurodevelopmental symptoms.</p><p><strong>Objective: </strong>This study aims to investigate the genetic etiology of a family with intellectual disability.</p><p><strong>Methods: </strong>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 <i>in silico</i> methods.</p><p><strong>Results: </strong>All four intellectual disability individuals carried the novel <i>AGO2</i> (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 <i>AGO2</i> and is predicted to affect the 3D structure of the <i>AGO2</i> protein.</p><p><strong>Conclusion: </strong>This study identifies a novel <i>AGO2</i> variant causing LESKRES in the Chinese population for the first time. Our findings expand the variants spectrum of <i>AGO2</i> leading to LESKRES and highlight the value of WES in diagnosing genetic causes of intellectual disabilities.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1598462"},"PeriodicalIF":2.8000,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198229/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of a novel <i>AGO2</i> variant causing LESKRES in a Chinese family with intellectual disability.\",\"authors\":\"Shufa Yang, Wei Song, Yousheng Yan\",\"doi\":\"10.3389/fgene.2025.1598462\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Lessel-Kreienkamp syndrome (LESKRES, MIM #619149), an autosomal dominant genetic disorder caused by variants in <i>AGO2</i> (MIM*606229), primarily leads to neurodevelopmental symptoms.</p><p><strong>Objective: </strong>This study aims to investigate the genetic etiology of a family with intellectual disability.</p><p><strong>Methods: </strong>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 <i>in silico</i> methods.</p><p><strong>Results: </strong>All four intellectual disability individuals carried the novel <i>AGO2</i> (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 <i>AGO2</i> and is predicted to affect the 3D structure of the <i>AGO2</i> protein.</p><p><strong>Conclusion: </strong>This study identifies a novel <i>AGO2</i> variant causing LESKRES in the Chinese population for the first time. Our findings expand the variants spectrum of <i>AGO2</i> leading to LESKRES and highlight the value of WES in diagnosing genetic causes of intellectual disabilities.</p>\",\"PeriodicalId\":12750,\"journal\":{\"name\":\"Frontiers in Genetics\",\"volume\":\"16 \",\"pages\":\"1598462\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-06-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198229/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3389/fgene.2025.1598462\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fgene.2025.1598462","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
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.
Frontiers in GeneticsBiochemistry, 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.