一个腓骨肌萎缩症4C型家系的SH3TC2基因突变分析

Mutation analysis for a family affected with Charcot-Marie-Tooth disease type 4C

目的明确1个腓骨肌萎缩症（Charcot—Marie—Toothdisease，CMT）家系的分子遗传发病机制。方法抽提家系成员外周血基因组DNA；应用目标外显子捕获及二代测序技术对先证者的72个候选基因进行基因突变筛查，并对可疑基因进行Sanger测序验证；用PyMOL-1软件对突变基因的蛋白质结构进行分子模拟。结果先证者SH3TC2基因第11外显子中检出C．1894G〉A纯合错义突变（P．E632K）；先证者父母及女儿均为C．1894G〉A杂合突变携带者，其他家系成员及300名正常对照者中均未检测到该突变。经检索NCBI、HGMD、1000genome等数据库，C．1894G〉A突变为未报道过的新突变。分子模拟显示该基因突变改变了SH3TC2蛋白的三维构象。结论SH3TC2基因突变可能与该CMT4C型家系先证者的发病有关。新发现的C．1894G〉A突变（p．E632K）扩展了SH3TC2基因的突变谱。

Objective To identify potential mutation in a Chinese family affected with Charcot-Marie- Tooth disease（CMT）. Methods Clinical data of the family was collected, and genomic DNA was extracted from peripheral blood samples of the family members. Seventy-two candidate genes of the proband were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. The protein structure was predicted with PyMOL-1 software. Results A homozygous missense mutation c. 1894G~ A（p. E632K） was identified in the exon 11 of the SH3TC2 gene in the proband. Heterozygous c. 1894G〉A mutation was also detected in the proband＇s father, mother and daughter, but not in the healthy family members and 300 normal controls. Retrieval of the NCBI, HGMD and 1000 genome databases has verified the c. 1894G〉 A to be as a novel mutation. Computer simulation has suggested that the mutation has altered the 3D structure of the SH3TC2 protein. Conclusion The proband was diagnosed as CMT4C, for which the underlying gene was SH3TC2. This finding has expanded the spectrum of SH3TC2 mutation in association with CMT4C.