一个先天性副肌强直家系SCN4A基因新突变

Paramyotonia congenita caused by a novel mutation of SCN4A gene in a Chinese family

目的对1个先天性副肌强直家系的SCN4A基因突变进行分析，为患者家系提供遗传咨询。方法收集该家系的临床资料，抽取先证者及7名家系成员的外周血提取基因组DNA，通过PCR-Sanger测序技术对先证者进行SCN4A基因突变的检测；同时在家系的3例患者、4名正常家系成员和100名无血缘关系的对照中对发现的突变进行检测。应用生物信息学软件预测突变对蛋白功能影响，并比对突变位点在不同物种间的保守性。结果先证者及家系中3例患者的SCN4A基因第24外显子均存在c．4427T〉C（p．Met1476Thr）杂合突变，而家系中4名表型正常成员和100名正常对照中均未发现该突变，经检索HGMD和SNP数据库证实该突变未见报道。生物信息学分析提示该突变可能影响蛋白结构和功能，突变氨基酸在不同物种间高度保守。结论SCN4A基因的C．4427T〉C（p．Metl476Thr）突变可能是该先天性副肌强直家系的致病原因。先天性副肌强直症临床表现缺乏特异性，基因突变检测是确诊该病的有效方法。

Objective To detect SCN4A gene mutation in a pedigree with paramyotonia congenita in order to facilitate genetic counseling and assisted reproduction. Methods Clinical data of the family was collected. DNA was extracted from peripheral blood samples. Potential mutation of the SCN4A gene was screened using PCR-Sanger sequencing. Potential mutation was detected in 3 affected relatives, 4 unaffected relatives and 100 unrelated healthy controls. Bioinformatics software was used to predict the effect of mutation on the protein function and conservation of the sequence at the mutation site across various species. Results A novel missense mutation c. 4427T〉C （p. Met1476Thr） was detected in the exon 24 of the SCN4A gene in the proband and other 3 affected relatives, but not in 4 unaffected relatives and 100 unrelated controls. Bioinformatic analysis indicated that the codon is highly conserved across various species, and that the mutation has caused damage to the structure and function of SCN4A protein. Conclusion The c. 4427 T〉C （p. Met1476Thr） mutation of the SCN4A gene may contribute to the paramyotonia congenita. Detection of SCN4A gene mutation is an effective method for the diagnosis of paramyotonic congenita.