Abstract
Background: Autosomal recessive cerebellar ataxias (ARCA) are heterogeneous, complex, disabling neurodegenerative diseases characterized by autosomal recessive inheritance and cerebellar ataxia. Numerous mutations are described in several populations. However, in China, few data are available concerning ARCA. In this study, we aimed to identify ARCA-associated ataxia by targeted next-generation sequencing or whole-exome sequencing in a Chinese cohort, trying to determine clinical and genetic characteristics of Chinese patients with ARCA.Results: We identified 15 different mutations in 7 unrelated patients, of which 12 were novel, including seven missense mutations, three frameshift mutations, two splicing mutations, two nonsense mutations, and one inframe deletion mutation. The most frequent gene was ATM (3 patients), followed by SACS (2 patients), SYNE1 (2 patients), and SETX (1 patient). Specifically, 1 patient harbored mutations in both ATM and SYNE1. The phenotype was mainly cerebellar ataxia in all these cases. However, peripheral neuropathy, dystonia, oculomotor abnormalities, pyramidal tract dysfunction, cognitive impairment, and epilepsy were also revealed. Patients who harbored different gene mutations showed mutational heterogeneity. Conclusions: Our results indicate that ARCA-associated gene mutations are uncommon with additional clinical features in the Chinese population, and advanced sequencing is required to aid the diagnosis of undetermined cerebellar ataxia in Chinese patients.