Novel mutation in the TOR1A (DYT1) gene in atypical, early onset dystonia and polymorphisms in dystonia and early onset parkinsonism

被引:134
作者
Leung, JC
Klein, C
Friedman, J
Vieregge, P
Jacobs, H
Doheny, D
Kamm, C
DeLeon, D
Pramstaller, PP
Penney, JB
Eisengart, M
Jankovic, J
Gasser, T
Bressman, SB
Corey, DP
Kramer, P
Brin, MF
Ozelius, LJ
Breakefield, XO [1 ]
机构
[1] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Boston, MA 02114 USA
[3] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany
[4] Mt Sinai Hosp, Movement Disorders Ctr, New York, NY 10029 USA
[5] Beth Israel Deaconess Med Ctr, Dept Neurol, New York, NY 10003 USA
[6] Reg Gen Hosp, Dept Neurol, Bolzano, Italy
[7] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA
关键词
early onset parkinsonism; Myoclonus-dystonia; TORIA (DYT1); Multiphor single-strand conformational polymorphism analysis; 18-bp deletion;
D O I
10.1007/s100480100111
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Dystonia is a movement disorder involving sustained muscle contractions and abnormal posturing with a strong hereditary predisposition and without a distinct neuropathology. In this study the TOR1A (DYT1) gene was screened for mutations in cases of early onset dystonia and early onset parkinsonism (EOP), which frequently presents with dystonic symptoms. In a screen of 40 patients, we identified three variations, none of which occurred in EOP patients. Two infrequent intronic single base pair (bp) changes of unknown consequences were found in a dystonia patient and the mother of an EOP patient. An 18-bp deletion (Phe323(-)Tyr328del) in the TOR1A gene was found in a patient with early onset dystonia and myoclonic features. This deletion would remove 6 amino acids close to the carboxy terminus, including a putative phosphorylation site of torsinA. This 18-bp deletion is the first additional mutation, beyond the GAG-deletion (Glu302/303del), to be found in the TOR1A gene, and is associated with a distinct type of early onset dystonia.
引用
收藏
页码:133 / 143
页数:11
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