Ozelius L J, Hewett J W, Page C E, Bressman S B, Kramer P L, Shalish C, de Leon D, Brin M F, Raymond D, Corey D P, Fahn S, Risch N J, Buckler A J, Gusella J F, Breakefield X O
Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston, USA.
Nat Genet. 1997 Sep;17(1):40-8. doi: 10.1038/ng0997-40.
Early-onset torsion dystonia is a movement disorder, characterized by twisting muscle contractures, that begins in childhood. Symptoms are believed to result from altered neuronal communication in the basal ganglia. This study identifies the DYT1 gene on human chromosome 9q34 as being responsible for this dominant disease. Almost all cases of early-onset dystonia have a unique 3-bp deletion that appears to have arisen idependently in different ethnic populations. This deletion results in loss of one of a pair of glutamic-acid residues in a conserved region of a novel ATP-binding protein, termed torsinA. This protein has homologues in nematode, rat, mouse and humans, with some resemblance to the family of heat-shock proteins and Clp proteases.
早发性扭转性肌张力障碍是一种运动障碍,其特征为扭转性肌肉挛缩,始于儿童期。症状被认为是由基底神经节中神经元通讯改变所致。本研究确定人类9号染色体q34上的DYT1基因是导致这种显性疾病的原因。几乎所有早发性肌张力障碍病例都有一个独特的3碱基对缺失,该缺失似乎在不同种族人群中独立出现。这种缺失导致一种名为扭转蛋白A的新型ATP结合蛋白保守区域中的一对谷氨酸残基之一丢失。这种蛋白质在秀丽隐杆线虫、大鼠、小鼠和人类中都有同源物,与热休克蛋白家族和Clp蛋白酶有一些相似之处。