一个骨骼肌钠离子通道病家系的临床特点和SCN4A基因变异分析

Analysis of SCN4A gene variation in a Chinese pedigree affected with skeletal muscle sodium channelopathies

目的对1个骨骼肌钠离子通道病家系进行临床特点和基因变异分析,并探讨SCN4A基因变异导致同一家系内正常血钾型周期性瘫痪和先天性副肌强直表型异质性的遗传学机制。方法应用高通量测序和Sanger测序技术进行SCN4A基因变异检测。结果该家系4例患者中,3例表现为正常血钾型周期性瘫痪,1例表现为先天性副肌强直。测序结果显示4例患者SCN4A基因第13外显子均检出c.2078T>C(p.Ile693Thr)变异,为已知致病性变异。结论SCN4A基因c.2078T>C(p.Ile693Thr)变异可导致家系中不同患者出现表型差异,表现为正常血钾型周期性瘫痪或先天性副肌强直。

Objective To explore the clinical features of a Chinese pedigree affected with skeletal muscle sodium channelopathies due to variation of SCN4A gene. Methods Potential variation of the 24 exons of the SCN4A gene was screened using PCR and Sanger sequencing. Results Four family members were affected with the disease in an autosomal dominant inheritance pattern. Three patients had normekalemic periodic paralysis, while 1 showed paramyotonia congenita. Genetic analysis detected a missense variation c. 2078T>C(p.Ile693Thr) in exon 13 of the SCN4A gene in the proband and other 3 affected relatives. Conclusion Normokalemic periodic paralysis and paramyotonia congenita can occur in different family members with skeletal muscle sodium channelopathies due to c. 2078T>C(p.Ile693Thr) variation of SCN4A gene.