CLCN1基因复合杂合突变导致先天性肌强直1例

A Case of Congenital Myotonia Caused by Compound Heterozygous Mutations in CLCN1 Gene

摘要: 目的：探讨1例由CLCN1基因复合杂合突变所致的Becker型先天性肌强直患儿的临床特征、辅助检查及治疗效果，为先天性肌强直的早期基因诊断及个体化治疗提供临床参考。方法：回顾性分析1例以“双下肢发僵2年”就诊的12岁男性患儿，收集其临床表现、实验室检查及肌电图结果，采用全外显子组测序检测CLCN1基因突变，并对父母进行家系验证。结果：患儿表现为肌强直(双下肢首发，逐渐累及上肢，握拳不能放松)、下肢肌肉肥大，血清肌酸激酶(320 U/L)轻度升高，肌电图提示典型的肌强直电位。基因检测发现，CLCN1基因c.1579A>C (p.Ile527Leu)和c.793_794delinsCT (p.Asp265Leu)复合杂合突变，分别遗传自母亲和父亲，且为首次报道的新型变异。经拉莫三嗪治疗6个月后，肌强直症状显著缓解，随访期间无药物不良反应，复查血清肌酸激酶降至280 U/L (恢复正常)。结论：该复合杂合突变位点考虑是患儿发病的原因，进一步扩展了先天性肌强直的致病突变谱，为临床早期诊断与临床管理提供参考。

Abstract: Objective: To investigate the clinical characteristics, auxiliary examinations and therapeutic effects of a child with Becker-type congenital myotonia caused by compound heterozygous mutations in the CLCN1 gene, so as to provide clinical references for the early genetic diagnosis and individualized treatment of congenital myotonia. Methods: A retrospective analysis was performed on a 12-year-old male child who presented with “stiffness in both lower limbs for 2 years”. Clinical manifestations, laboratory tests, and electromyography (EMG) results were collected. Whole-exome sequencing was used to detect CLCN1 gene mutations, and familial verification was conducted for the parents. Results: The child presented with myotonia (first affecting both lower limbs, gradually involving the upper limbs with inability to relax clenched fists), muscle hypertrophy in the lower limbs, mildly elevated serum creatine kinase (320 U/L), and electromyography (EMG) indicated typical myotonic potentials. Genetic testing revealed compound heterozygous mutations in the CLCN1 gene: c.1579A>C (p.Ile527Leu) and c.793_794delinsCT (p.Asp265Leu), inherited from the mother and father, respectively, which were novel variants reported for the first time. After 6 months of treatment with lamotrigine, the myotonic symptoms were significantly relieved, no adverse drug reactions occurred during follow-up, and the rechecked serum creatine kinase decreased to 280 U/L (returning to normal). Conclusion: The compound heterozygous mutation sites are considered to be the cause of the onset of the disease in the child, which further expands the pathogenic mutation spectrum of congenital myotonia and provides a reference for clinical early diagnosis and clinical management.