Shiqi Fan, Shuanghao Yang, Xiaojing Nie, Zhihua Yu, Yan Jiang, Miao Sun, Weiyue Gu, Xue Zhang
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Reanalysis of Whole Genome Sequencing Resolves Genetically Undiagnosed Patients With "RNUopathies".
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."
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