A case of autosomal recessive myotonia congenita due to compound heterozygous mutations c.1388del and c.1679T>C in the CLCN1 gene
10.3760/cma.j.cn113694-20240906-00610
- VernacularTitle:CLCN1基因c.1388del和c.1679T>C复合杂合突变致常染色体隐性先天性肌强直1例
- Author:
Wenjuan HAN
1
;
Yurong HU
1
;
Yan ZHANG
1
;
Rena ABUDUSALAMU
1
;
Dengfeng HAN
1
Author Information
1. 新疆医科大学第一附属医院神经内科，乌鲁木齐 830054
- Publication Type:Journal Article
- Keywords:
Myotonia congenita;
Autosomal recessive;
CLCN1 gene;
Compound heterozygous mutation
- From:
Chinese Journal of Neurology
2025;58(4):414-418
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical characteristics, auxiliary examinations, and genetic mutations of a patient with myotonia congenita (MC).Methods:A retrospective analysis was conducted on the clinical data and whole exome sequencing results of a patient who visited the Department of Neurology, the First Affiliated Hospital of Xinjiang Medical University on April 13, 2023, and her family members. Candidate variants were verified by Sanger sequencing.Results:The patient was a 30-year-old female who presented with muscle stiffness and transient weakness during the transition from rest to movement since childhood, which improved after repeated limb movements. With age, involvement of upper limb skeletal muscles, extraocular muscles, and masticatory muscles was noted. Electromyography (EMG) showed abundant myotonic potentials in the muscles of the limbs, and serum creatine kinase levels (586.80 IU/L) were elevated. Genetic testing revealed that the patient carried 2 mutations in the CLCN1 gene: a newly discovered single nucleotide deletion mutation c.1388del (p.Phe463SerfsTer4), and a known missense mutation c.1679T>C (p.Met560Thr). These mutations were present in a compound heterozygous state. The patient′s father carried the c.1388del single heterozygous mutation, while her mother, son, aunt, younger uncle, and grandmother carried the c.1679T>C single heterozygous mutation. Conclusions:MC is primarily characterized by muscle stiffness and transient weakness at the onset of movement, which improves after "warm-up". The proband in this pedigree exhibits typical MC symptoms, with significantly elevated creatine kinase levels and EMG revealing abundant myotonic potentials in the muscles of the limbs indicating myopathic damages. The new mutation c.1388del (p.Phe463SerfsTer4) in the CLCN1 gene further expands the spectrum of pathogenic mutations in the CLCN1 gene.
