Whole-exome sequencing detects PYGM variants in two adults with McArdle disease.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2022-03-24 Print Date: 2022-02-01 DOI:10.1101/mcs.a006173

Amanda Thomas-Wilson, Avinash V Dharmadhikari, Jonas J Heymann, Vaidehi Jobanputra, Salvatore DiMauro, Michio Hirano, Ali B Naini, Mythily Ganapathi

引用次数: 0

Abstract

McArdle disease is a debilitating glycogen storage disease with typical onset in childhood. Here, we describe a former competitive athlete with early adult-onset McArdle disease and a septuagenarian with a history of exercise intolerance since adolescence who was evaluated for proximal muscle weakness. Exome sequencing identified biallelic variants in the PYGM gene for both cases. The former athlete has the common, well-known pathogenic variant p.(Arg50Ter) in trans with a novel missense variant, p.(Asp694Glu). The second individual has a previously described homozygous missense variant, p.(Arg771Gln). Here, we describe the clinical course, enzyme-testing results using muscle tissue, and molecular findings for the individuals and add to the knowledge of the genotypic spectrum of this disorder.

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全外显子组测序检测PYGM变异在两个成人麦卡德尔病。

麦卡德尔病是一种使人衰弱的糖原贮存病，典型发病于儿童期。在这里，我们描述了一位患有早期成人发病的麦卡德尔病的前竞技运动员和一位从青春期开始就有运动不耐受史的七十多岁的人，他被评估为近端肌肉无力。外显子组测序鉴定出两例患者的PYGM基因双等位变异。这位前运动员有常见的、众所周知的致病变异p.(Arg50Ter)反式和一种新的错义变异p.(Asp694Glu)。第二个个体具有先前描述的纯合错义变体p.(Arg771Gln)。在这里，我们描述了临床过程，使用肌肉组织的酶检测结果，以及个体的分子发现，并增加了这种疾病的基因型谱的知识。

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

Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.20

自引率

0.00%

发文量

期刊介绍： Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.