Price Emma, Fedida Liron M, Pugacheva Elena M, Ji Yon J, Loukinov Dmitri, Lobanenkov Victor V
Molecular Pathology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Front Mol Neurosci. 2023 May 31;16:1185796. doi: 10.3389/fnmol.2023.1185796. eCollection 2023.
-related disorder (CRD) is a neurodevelopmental disorder (NDD) caused by monoallelic pathogenic variants in . The first variants in CRD cases were documented in 2013. To date, 76 variants have been further described in the literature. In recent years, due to the increased application of next-generation sequencing (NGS), growing numbers of variants are being identified, and multiple genotype-phenotype databases cataloging such variants are emerging.
In this study, we aimed to expand the genotypic spectrum of CRD, by cataloging NDD phenotypes associated with reported variants. Here, we systematically reviewed all known variants reported in case studies and large-scale exome sequencing cohorts. We also conducted a meta-analysis using public variant data from genotype-phenotype databases to identify additional variants, which we then curated and annotated.
From this combined approach, we report an additional 86 variants associated with NDD phenotypes that have not yet been described in the literature. Furthermore, we describe and explain inconsistencies in the quality of reported variants, which impairs the reuse of data for research of NDDs and other pathologies.
From this integrated analysis, we provide a comprehensive and annotated catalog of all currently known mutations associated with NDD phenotypes, to aid diagnostic applications, as well as translational and basic research.
-相关疾病（CRD）是一种由单等位基因致病变异引起的神经发育障碍（NDD）。CRD病例中的首批致病变异于2013年被记录下来。迄今为止，已有76个致病变异在文献中得到进一步描述。近年来，由于下一代测序（NGS）应用的增加，越来越多的致病变异被识别出来，并且出现了多个编目此类变异的基因型-表型数据库。
在本研究中，我们旨在通过编目与已报道的致病变异相关的NDD表型来扩展CRD的基因型谱。在此，我们系统地回顾了病例研究和大规模外显子测序队列中报道的所有已知致病变异。我们还使用来自基因型-表型数据库的公共变异数据进行荟萃分析，以识别其他致病变异，然后对其进行整理和注释。
通过这种综合方法，我们报告了另外86个与尚未在文献中描述的NDD表型相关的致病变异。此外，我们描述并解释了所报道变异质量的不一致性，这损害了用于NDD和其他病理学研究的数据重用。
通过这种综合分析，我们提供了一份全面且经过注释的与NDD表型相关的所有当前已知突变目录，以辅助诊断应用以及转化研究和基础研究。
