多巴反应性肌张力障碍酪氨酸羟化酶基因的一个新致病突变

A novel pathological mutation of tyrosine hydroxylase gene in dopa-responsive dystonia

目的 探讨1例无家族史的多巴反应性肌张力障碍患者的基因突变及临床特征.方法 收集1例无家族史的多巴反应性肌张力障碍患者的临床资料,并应用二代测序技术对其进行基因分析.结果 患者临床表现为轻中度缺陷型（A型）的酪氨酸羟化酶缺乏症;基因测序结果发现,患者酪氨酸羟化酶基因存在1个复合杂合突变：c.457C＞T导致氨基酸改变p.R153X,为已报道的致病无义突变;c.734G＞T导致氨基酸改变p.R245M,为未报道的错义突变,软件预测c.734G＞T很可能具有致病性.结论 c.734G＞T可能是1个酪氨酸羟化酶基因新的致病突变。

Objective To explore the clinical characteristics and gene mutation in a patient clinically diagnosed as dopa-responsive dystonia （DRD） without family history.Methods The clinical characteristics of a patient clinically diagnosed as DRD without family history were collected and molecular and bioinformatic analyses were performed.Results The patient demonstrated as type A tyrosine hydroxylase deficiency and a compound heterozygous mutation of tyrosine hydroxylase （TH） gene was found,including a known nonsense mutation,c.457C〉T and a novel missense mutation,c.734G〉T that was probably pathologically predicted by bioinformatic analysis.Conclusion c.734G〉T may be a novel pathological mutation of TH gene.