IRCCS Casa Sollievo della Sofferenza, CSS-Mendel Institute, Rome, Italy.
Mov Disord. 2009 Dec 15;24(16):2424-7. doi: 10.1002/mds.22861.
Mutations in the THAP1 gene on chromosome 8p21-p22 (DYT6 locus) have been recently reported as causative of autosomal dominant primary torsion dystonia (PTD) in four Amish-Mennonite families and in 12 additional probands of different ancestry. We sequenced the THAP1 gene in 158 patients with DYT1-negative PTD who had onset of symptoms below 30 years and/or positive family history. One sporadic Greek male patient, aged 57 years, was found to carry a novel heterozygous missense variant in THAP1 exon 3 (p.Cys170Arg), of likely pathogenic significance. This subject first presented with right writer's cramp at age of 10 years and, subsequently, developed left arm dystonia and an extremely severe left laterocollis, without further spreading to other body districts. Our findings expand the genotypic spectrum of THAP1 and strengthen the association with upper body involvement, including the cranial and cervical districts that are usually spared in DYT1-PTD.
最近有研究报道，8p21-p22 染色体上的 THAP1 基因突变（DYT6 基因座）是四个阿米什-门诺派家族和 12 名其他不同家族史的常染色体显性原发性扭转痉挛（PTD）患者的致病原因。我们对 158 名发病年龄小于 30 岁和/或有阳性家族史的 DYT1 阴性 PTD 患者进行了 THAP1 基因测序。我们发现一名希腊散发病例男性患者携带 THAP1 外显子 3 中的一种新型杂合错义变异（p.Cys170Arg），可能具有致病性。该患者首次出现右侧书写痉挛，年龄为 10 岁，随后发展为左臂肌张力障碍和极其严重的左侧斜颈，但未进一步扩散至其他身体部位。我们的研究结果扩展了 THAP1 的基因型谱，并加强了与上半身受累的关联，包括 DYT1-PTD 通常不受累的颅颈区。
