Abstract：
A Japanese woman experienced slowness of movement in her early teens and difficulty in opening her hands during pregnancy. On admission to our hospital at 42 years of age, she showed grip myotonia with warm-up phenomenon. However, she had neither muscle weakness, muscle atrophy, cold-induced symptomatic worsening nor episodes of transient weakness of the extremities. Needle electromyography of the first dorsal interosseous and anterior tibial muscles demonstrated myotonic discharges. Whole exome sequencing of the patient revealed a heterozygous single-base substitution in the CLCN1 gene (c.1028T>G, p.F343C). The same substitution was identified in affected members of her family (mother and brother) by Sanger sequencing, but not in healthy family members (father and a different brother). We diagnosed myotonia congenita (Thomsen disease) with a novel CLCN1 mutation in this pedigree. This mutation causes a single amino acid substitution in the I-J extracellular loop region of CLCN1. Amino acid changes in the I-J loop region are rare in an autosomal-dominantly inherited form of myotonia congenita. We think that this pedigree is precious to understand the pathogenesis of myotonia congenita.
摘要：
一名日本妇女在十几岁时运动缓慢，在怀孕期间难以张开双手。42岁时入院时，她表现出抓握肌强直和热身现象。然而,她没有肌肉无力,肌肉萎缩,寒冷引起的症状恶化或短暂的四肢无力发作。第一背侧骨间和胫骨前肌的针状肌电图显示肌强直放电。患者的全外显子组测序显示CLCN1基因中存在杂合单碱基置换（c.1028T>G，p.F343C)。通过Sanger测序，在受影响的家庭成员（母亲和兄弟）中发现了相同的替代，但不是健康的家庭成员（父亲和不同的兄弟）。我们在该谱系中诊断出先天性肌强直（汤姆森病）具有新的CLCN1突变。该突变导致CLCN1的I-J胞外环区中的单个氨基酸取代。I-J环区的氨基酸变化在先天性肌强直的常染色体显性遗传形式中很少见。我们认为，该家谱对于理解先天性肌强直症的发病机制非常宝贵。
