Identifying SYNE1 ataxia and extending the mutational spectrum in Korea.

INTRODUCTION: Recent advances in next generation sequencing technologies have uncovered the genetic background of various diseases. The mutations in the SYNE1 gene was previously identified as a potential cause of pure cerebellar ataxia. Although autosomal recessive ataxias are slightly more frequent than autosomal dominant forms worldwide, autosomal recessive forms are extremely rare in Korea. In this study, we aimed to identify SYNE1-associated ataxia by whole exome sequencing in a Korean sample, and to review the prevalence of SYNE1 in non-French-Canadians.

METHODS: Patients with suspected cerebellar ataxia who visited movement disorders clinic from March 2014 to December 2017 were clinically screened. After excluding cases with acquired causes and common genetic causes in Korea, including spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy, 63 undiagnosed subjects were screened for SYNE1 mutations by next generation sequencing methods.

RESULTS: We identified four novel mutations (one splicing, one truncating, and two missense mutations) distributed throughout the SYNE1 gene in two patients. The phenotype was mainly pure cerebellar ataxia in both cases. However, axonal neuropathy, mild frontal dysfunction, and autonomic dysfunction were also revealed. The age of disease onset was relatively late and the disease course was only mildly progressive.

CONCLUSION: Our results indicate that SYNE1 mutations are not an uncommon cause of recessive ataxia with additional clinical features in the Korean population. The results of this study should alert neurologists to request SYNE1 testing to aid the diagnosis of undetermined adult-onset ataxia in Korean patients.