GCH1基因新的点突变的多巴反应性肌张力障碍1例报道并文献复习

A novel missense mutation in GCH1 gene in a case of dopa-responsive dystonia and literature review

目的报道1例多巴反应性肌张力障碍(Doparesponsive dystonia,DRD)的三磷酸鸟苷环化水解酶I基因(Guanosine triphosphate cyclohydmlase I,GCH1)c.550C>T(p.R184C)杂合突变,并分析该基因突变患者的临床特点。方法应用全外显子测序结合一代测序验证方法对1个家系的5名成员进行GCH1基因突变分析,并回顾既往文献进行疾病特点总结,以提高对DRD相关基因突变的临床特点及预后的认识。结果5名家系成员中先证者及其一子一女GCH1基因存在c.550C>T(p.R184C)杂合突变,且该点突变导致GCH1基因所编码的蛋白发生p.R184C错义突变(184位点上的精氨酸变为半胱氨酸)。软件分析显示c.550C>T(p.R184C)为可疑致病突变。结论c.550C>T(p.R184C)突变可能是DRD新的致病位点,此分析扩展了DRD的GCH1基因突变内容,同时也为相关基因的功能验证提供了新的方向。

Objective To explore genetic mutations and clinical features of a pedigree affected with dopa-responsive dystonia.Methods PCR and Sanger sequencing were applied to detect mutations of the GCH1 gene among 5 members from the pedigree.Meanwhile,the characteristic of the onset of the disease,therapeutic and prognosis based on other studies were analyzed.Results A novel missense mutation c.550 C>T(p.R184 C)in exon of the GCH1 gene in a sporadic case was identified,which would lead to a transition at codon 184 from an Arginine to a Cysteine(p.R184 C).In silico analysis,the c.550 C>T(p.R184 C)mutation was predicted as probably pathological.Conclusion The c.550 C>T(p.R184 C)mutation probably underlied the disease in this pedigree.and expanded the spectrum of GCH1 gene mutation in DRD patients.