Reanalysis of Whole Genome Sequencing Resolves Genetically Undiagnosed Patients With "RNUopathies".

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Shiqi Fan, Shuanghao Yang, Xiaojing Nie, Zhihua Yu, Yan Jiang, Miao Sun, Weiyue Gu, Xue Zhang
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引用次数: 0

Abstract

Neurodevelopmental disorders (NDD) are a group of complex conditions characterized by marked phenotypic heterogeneity, primarily involving impairments in cognitive, emotional, and motor development. Approximately 40%-60% of patients with rare NDD remain genetically undiagnosed. Recently, RNU2-2 and RNU5B-1 have been identified as novel genes underlying the "RNUopathies" a syndromic NDD caused by variants in non-coding spliceosomal genes. In this study, we aimed to focus on RNU2-2 and RNU5B-1 by analyzing the whole-genome sequencing (WGS) data from 18326 Chinese individuals (including 2970 trios and 9416 samples without parental data), among whom 4900 had confirmed NDD phenotypes. Reanalysis of WGS data solved the previously undiagnosed cases of four patients with NDD carrying de novo variants in RNU genes, including three patients carrying the RNU2-2 variants (two cases with n.4G>A and one case with n.35A>G), and one case with an unreported RNU5B-1 variant (n.38C>T). In this study, detailed phenotypic elaboration and comparison with previous studies help clinicians in more effective diagnosis of NDD and underscore the importance of reanalyzing negative genetic data, which deepens our understanding of the "RNUopathies."

全基因组测序的再分析解决了遗传上未确诊的“RNUopathies”患者。
神经发育障碍(NDD)是一组以显著的表型异质性为特征的复杂疾病,主要涉及认知、情感和运动发育障碍。大约40%-60%的罕见NDD患者仍未得到基因诊断。最近,RNU2-2和RNU5B-1已被确定为“rnu病”的新基因,rnu病是由非编码剪接体基因变异引起的综合征性NDD。在这项研究中,我们通过分析来自18326个中国人(包括2970个三人组和9416个无亲本数据的样本)的全基因组测序(WGS)数据,重点研究RNU2-2和RNU5B-1,其中4900个已确认NDD表型。WGS数据的重新分析解决了先前未确诊的4例携带RNU基因新变体的NDD患者,其中3例携带RNU2-2变体(2例携带n.4G>A, 1例携带n.35A>G), 1例携带未报道的RNU5B-1变体(n.38C>T)。在这项研究中,详细的表型阐述和与以往研究的比较有助于临床医生更有效地诊断NDD,并强调重新分析阴性遗传数据的重要性,这加深了我们对“RNUopathies”的理解。
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
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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