A rare variant in TOR1A exon 5 associated with isolated dystonia in southwestern Chinese

ABSTRACT

Background: TOR1A has been proposed as an important genetic factor in early-onset isolated dystonia. Variants located in the 3′ untranslated region of TOR1A are of particular importance because they may influence gene expression, although related studies are limited. The objectives of the present study focused on variants in the TOR1A 3′ untranslated region.

Methods: The last exon of TOR1A was sequenced in 229 cases with isolated dystonia and in 210 controls. In addition, 471 controls were tested to determine the frequency of the variants in the 3′ untranslated region.

Results: Except for c.904_906delGAG, 3 rare sequence variants (NM_000113.2:c.*454T>A, NM_000113.2:c.860C>A [rs766483672], and NM_000113.2:c.*302T>A [rs563498119]) were found only in the patients. The c.*302T>A variant was located in the conserved region of the human microRNA (hsa-miR-494) binding site. A luciferase reporter assay showed that c.*302T>A significantly altered gene expression.

Conclusions: Population frequencies, computational analyses, and function experiments in this study implied that c.*302T>A is associated with dystonia.

Movement Disorders 2017