VPS13A基因突变致舞蹈病-棘红细胞增多症的诊断及家系研究

Diagnosis and Family Study of Chorea-Acanthocytosis Induced by VPS13A Gene Mutation

目的:探讨舞蹈病-棘红细胞增多症(Ch Ac)的诊断方法及家系特点,为Ch Ac的精准诊断提供可行合理的策略。方法:选取1例临床疑似Ch Ac患者(先证者)作为研究对象,收集其临床资料和家系资料并绘制遗传家系图;采用扫描电镜检测棘红细胞,利用全外显子目标序列捕获2代测序技术筛查Ch Ac易患性基因及其突变类型。结果:先证者主要临床表现为不自主伸舌、磨牙、扮鬼脸、头部及四肢舞蹈动作及口唇自噬动作,外周血肌酶和转氨酶均增高,头颅MRI可见尾状核轻度萎缩;其兄生前具有与先证者同样的临床表现,其父母及姐姐均体健;先证者外周血检测到典型棘红细胞,检测出液泡蛋白分类同源物13A(VPS13A)基因,且VPS13A基因存在c. 9403C> T纯合突变,引起氨基酸改变p. R3135X,为无义突变;先证者的父亲和母亲均为c. 9403C> T杂合突变。结论:结合临床表现及扫描电镜检查可以高度怀疑Ch Ac,但全外显子目标序列捕获2代测序技术可准确检测VPS13A基因突变,并可结合遗传家系特点,作为Ch Ac首选确诊手段。

Objective:To explore the diagnosis method and family characteristics of chorea-acanthocytosis(ChAc),and provide feasible and reasonable strategies for accurate diagnosis of ChAc.Methods:A clinically suspected ChAc patient(proband)was selected as the study object,the clinical and family datas of the proband were collected and a genetic family map was drawn.Then,acanthocytes were detected by scanning electron microscopy,and the susceptibility genes and mutation types of ChAc were screened by total exon target sequence capture next-generation sequencing technology.Results:The main clinical manifestations of this proband were involuntary tongue extension,molar grinding,grimace,head and limb dance movements,and lip autophagy.Creatine kinase and aminotransferases were increased,brain MRI showed slight atrophy of the caudate nucleus.His brother had the same clinical manifestations as the proband before his death,and his parents and sister were healthy.Typical acanthocytes were detected by scanning electron microscopy in peripheral blood.More importantly,the vacuolar protein sorting homolog 13 A(VPS13A)gene was detected,and there was c.9403C>T homozygous mutation in VPS13A gene,which caused changes in p.R3135X,thereby it was a nonsense mutation;his parents displayed a heterozygous mutation of the same genetic mutation.Conclusion:ChAc can be highly suspected by clinical data and acanthocytes.However,total exon target sequence capture next-generation sequencing technology can accurately detect VPS13A gene mutation,and can be combined with the characteristics of genetic families.Therefore,it can be used as the first choice for diagnosis of ChAc.