Analysis of clinical and genetic features of congenital myasthenic syndrome type 10 caused by DOK7 gene mutations
10.3760/cma.j.cn113694-20240209-00089
- VernacularTitle:DOK7基因突变所致先天性肌无力综合征10型的临床表型和基因型特征分析
- Author:
Huixia LIN
1
;
Jie CHEN
;
Ruijuan SHA
Author Information
1. 南京医科大学附属脑科医院神经内科，南京 210029
- Keywords:
Myasthenic syndrome, congenital;
DOK7 gene;
Genotype;
Phenotype
- From:
Chinese Journal of Neurology
2024;57(11):1239-1246
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the phenotype and genotype of congenital myasthenic syndrome type 10 (CMS10) caused by DOK7 gene mutation, and to conduct a literature review and summary of this disease. Methods:A retrospective analysis of the clinical characteristics and genetic test results of a patient with CMS10 in Affiliated Nanjing Brain Hospital, Nanjing Medical University in January 2020 was conducted. Whole exon sequencing was applied to high-throughput screen the pathogenic gene in this patient. After finding candidate variants, pathogenic classification was done according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline. Sanger sequencing was applied to verify the mutation. Then all patients with DOK7 gene mutations were summarized by searching the literatures through PubMed, CNKI and Wanfang database. Results:The patient was a 51-year-old man who clinically presented with fluctuating quadriparesis and respiratory distress. He was diagnosed as CMS10 with compound mutations in DOK7 (c.1296_1311del16/c.332-1G>A) by clinical information and whole exon and Sanger sequencing. And c.332-1G>A was found to be a novel mutation. Literature review showed that patients with CMS10 with DOK7 gene mutations presented dominant weakness in proximal limbs and axial muscles. Patients with CMS10 would show periodic exacerbation in disease duration with slow progression. Among 71 mutations, frameshift mutation was the most frequent type (38.0%, 27/71), followed by missense mutation (32.4%, 23/71). Exon 7 (35.2%, 25/71) and exon 4 (26.8%, 19/71) were the hotspot regions. c.1124_1127dupTGCC was the most frequent mutation (43.2%, 140/324). The age of onset in patients with homozygous c.1124_1127dupTGCC was older than that in patients with compound heterozygous c.1124_1127dupTGCC [7.5(3.6, 19.8) years vs 1.3(0, 3.8) years, U=350.000, P<0.001]. Conclusions:CMS10 is a slowly progressive autosomal recessive genetic disease characterized by fluctuating muscle weakness, with muscle weakness distribution similar to limb-girdle muscular dystrophy. Frameshift mutation is the most common type in DOK7 gene associated CMS10. c.1124_1127dupTGCC in C-terminal is the most frequent mutation. Early identification of DOK7 gene associated CMS10 is crucial for the treatment and prognosis of this disease.
