Whole-exome sequencing in a cohort of Chinese patients with isolated cervical dystonia.

Background: Dystonia is a kind of movement disorder but its pathophysiological mechanisms are still largely unknown. Recent evidence reveals that genetical defects may play important roles in the pathogenesis of dystonia.

Objectives And Methods: -To explore possible causative genes in Chinese dystonia patients, DNA samples from 42 sporadic patients with isolated cervical dystonia were subjected to whole-exome sequencing. Rare deleterious variants associated with dystonia phenotype were screened out and then classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Phenolyzer was used for analyzing the most probable candidates correlated with dystonia phenotype, and SWISS-MODEL server was for predicting the 3D structures of variant proteins.

Results: Among 42 patients (17 male and 25 female) recruited, a total of 36 potentially deleterious variants of dystonia-associated genes were found in 30 patients (30/42, 71.4 %). Four disease-causing variants including a pathogenic variant in (c.797G > C) and three likely pathogenic variants in (c.73C > T), (c.1A > C) and (c.56C > G) were found in four patients separately. Other 32 variants were classified as uncertain significance in 26 patients. Phenolyzer prioritized genes , and as the most probable candidates correlated with dystonia phenotype. Although 3D prediction of and variant proteins detected no obvious structural alterations, the mutation in (c.73C > T:p.Arg25Trp) was closely adjacent to its key functional domain.

Conclusion: Our whole-exome sequencing results identified a novel variant in in sporadic Chinese patients with isolated cervical dystonia, which however, needs our further study on its exact role in dystonia pathogenesis.