Case report: exome sequencing achieved a definite diagnosis in a Chinese family with muscle atrophy

BMC Neurology

Jingxin Pan¹  Chunmiao Guo²  Yibin Guo³  Ying Huang⁴  Hui Jiang⁴  Jie Xie⁴  Miaoxin Li⁵ 

[1] Department of Hematology, The Second Affiliated Hospital, Fujian University of Medical Science, 362000, Quanzhou, China;Department of Neurology, The Second Affiliated Hospital, Fujian University of Medical Science, 362000, Quanzhou, China;Key Laboratory of Tropical Diseases Control (SYSU), Sun Yat-sen University, 510080, Guangzhou, China;Center for Precision Medicine, Sun Yat-sen University, 510080, Guangzhou, China;School of Medicine, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China;Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, China;Key Laboratory of Tropical Diseases Control (SYSU), Sun Yat-sen University, 510080, Guangzhou, China;Center for Precision Medicine, Sun Yat-sen University, 510080, Guangzhou, China;Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, China;Key Laboratory of Tropical Diseases Control (SYSU), Sun Yat-sen University, 510080, Guangzhou, China;Center for Precision Medicine, Sun Yat-sen University, 510080, Guangzhou, China;The Fifth Affiliated Hospital, Sun Yat-sen University, 519000, Zhuhai, Guangdong, China;State Key Laboratory for Cognitive and Brain Sciences, The University of Hong Kong, Hong Kong SAR, China;

关键词: Exome sequencing;    Diagnosis;    GDAP1;    Charcot-Marie-tooth type 4A;    Muscle atrophy;    Case report;   

DOI  :  10.1186/s12883-021-02093-z

来源: Springer

【 摘 要 】

BackgroundDue to large genetic and phenotypic heterogeneity, the conventional workup for Charcot-Marie-Tooth (CMT) diagnosis is often underpowered, leading to diagnostic delay or even lack of diagnosis. In the present study, we explored how bioinformatics analysis on whole-exome sequencing (WES) data can be used to diagnose patients with CMT disease efficiently.Case presentationThe proband is a 29-year-old female presented with a severe amyotrophy and distal skeletal deformity that plagued her family for over 20 years since she was 5-year-old. No other aberrant symptoms were detected in her speaking, hearing, vision, and intelligence. Similar symptoms manifested in her younger brother, while her parents and her older brother showed normal. To uncover the genetic causes of this disease, we performed exome sequencing for the proband and her parents. Subsequent bioinformatics analysis on the KGGSeq platform and further Sanger sequencing identified a novel homozygous GDAP1 nonsense mutation (c.218C > G, p.Ser73*) that responsible for the family. This genetic finding then led to a quick diagnosis of CMT type 4A (CMT4A), confirmed by nerve conduction velocity and electromyography examination of the patients.ConclusionsThe patients with severe muscle atrophy and distal skeletal deformity were caused by a novel homozygous nonsense mutation in GDAP1 (c.218C > G, p.Ser73*), and were diagnosed as CMT4A finally. This study expanded the mutation spectrum of CMT disease and demonstrated how affordable WES could be effectively employed for the clinical diagnosis of unexplained phenotypes.

【 授权许可】

CC BY