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Mov Disord. 2014 Jul;29(8):1079-83. doi: 10.1002/mds.25921. Epub 2014 May 23.

Combined occurrence of a novel TOR1A and a THAP1 mutation in primary dystonia.

Author information

1
Department of Medical Genetics, University of Tuebingen, 72076, Germany; Department of Neurology, the First Hospital of Jilin University, Changchun, PR China.

Abstract

BACKGROUND:

The ΔGAG 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 ΔGAG 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.

KEYWORDS:

DYT1/TOR1A mutation; DYT6/THAP1 mutation; dual luciferase assay; primary dystonia; subcellular distribution

PMID:
24862462
DOI:
10.1002/mds.25921
[Indexed for MEDLINE]

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