Combined occurrence of a novel TOR1A and a THAP1 mutation in primary dystonia.
Cheng, Fu-Bo MD 1,2; Feng, Jia-Chun MD 2; Ma, Ling-Yan MD 3; Miao, Jing MD 2; Ott, Thomas PhD 1; Wan, Xin-Hua MD 3; Grundmann, Kathrin MD 1
[Report] Movement Disorders. 29(8):1079-1083, July 2014.

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Background: The [DELTA]GAG deletion of the TOR1A gene (DYT1) is responsible for DYT1 dystonia. However, no other TOR1A mutation has been reported in the Chinese population.

Methods: Two hundred one dystonia patients without the [DELTA]GAG deletion were screened for other mutations in TOR1A. Gene function changes were analyzed by subcellular distribution and luciferase reporter assay.

Results: A novel TOR1A mutation (c.581A>T, p.Asp194Val) was found in a patient with early-onset segmental dystonia harboring a THAP1 mutation (c.539T>C, p.Leu180Ser). Overexpression of mutant TOR1A Asp194Val protein induces inclusion formation in SK-N-AS cell lines, and the repressive activity of the mutant THAP1 Leu180Ser protein on TOR1A gene expression is decreased compared with wild-type THAP1.

Conclusions: This is the first report about a dystonia patient harboring two distinct dystonia gene mutations. Functional analysis indicated a potential additive effect of these two mutations, which might provoke the occurrence of dystonic symptoms in this patient. (C) 2014 International Parkinson and Movement Disorder Society

(C) 2014 John Wiley & Sons, Ltd