Neuroimaging to Genotype: Delineating the Spectrum of Disorders With Deficient Myelination in the Indian Population.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-10-29 DOI:10.1002/ajmg.a.63914

Namanpreet Kaur, Michelle C do Rosario, Purvi Majethia, Selinda Mascarenhas, Lakshmi Priya Rao, Karthik Vijay Nair, Bhagesh Hunakunti, Adarsh Pooradan Prasannakumar, Rohit Naik, Dhanya Lakshmi Narayanan, Shalini S Nayak, Vivekananda Bhat, Suvasini Sharma, Y Ramesh Bhat, B L Yatheesha, Rajesh Kulkarni, Siddaramappa J Patil, Sheela Nampoothiri, Shahyan Siddiqui, Katta Mohan Girisha, Stephanie Bielas, Anju Shukla

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Abstract

Several genetic disorders are associated with either a permanent deficit or a delay in central nervous system myelination. We investigated 24 unrelated families (25 individuals) with deficient myelination after clinical and radiological evaluation. A combinatorial approach of targeting and/or genomic testing was employed. Molecular diagnosis was achieved in 22 out of 24 families (92%). Four families (4/9, 44%) were diagnosed with targeted testing and 18 families (18/23, 78%) were diagnosed using broad genomic testing. Overall, 14 monogenic disorders were identified. Twenty disease-causing variants were identified in 14 genes including PLP1, GJC2, POLR1C, TUBB4A, UFM1, NKX6-2, DEGS1, RNASEH2C, HEXA, ATP7A, SETBP1, GRIN2B, OCLN, and ZBTB18. Among these, nine (45%) variants are novel. Fourteen families (82%, 14/17) were diagnosed using proband-only exome sequencing (ES) complemented with deep phenotyping, thus highlighting the utility of singleton ES as a valuable diagnostic tool for identifying these disorders in resource-limited settings.

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从神经成像到基因型：划定印度人群髓鞘缺失症的范围

有几种遗传疾病与中枢神经系统髓鞘化永久性缺失或延迟有关。经过临床和放射学评估，我们对 24 个髓鞘缺失的非亲缘家庭（25 人）进行了调查。我们采用了靶向和/或基因组检测的组合方法。24 个家族中有 22 个（92%）获得了分子诊断。4个家庭（4/9，44%）通过靶向检测确诊，18个家庭（18/23，78%）通过广泛的基因组检测确诊。总体而言，共发现了 14 种单基因疾病。在 14 个基因中发现了 20 个致病变体，包括 PLP1、GJC2、POLR1C、TUBB4A、UFM1、NKX6-2、DEGS1、RNASEH2C、HEXA、ATP7A、SETBP1、GRIN2B、OCLN 和 ZBTB18。在这些变异中，有 9 个（45%）是新变异。有14个家庭（82%，14/17）是通过仅进行探针外显子组测序（ES）并辅以深度表型分析而确诊的，从而凸显了单基因外显子组测序作为一种有价值的诊断工具在资源有限的环境中鉴别这些疾病的实用性。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.