Autosomal Recessive Cerebellar Ataxia Type 1: Phenotypic and Genetic Correlation in a Cohort of Chinese Patients with SY
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ORIGINAL ARTICLE
Autosomal Recessive Cerebellar Ataxia Type 1: Phenotypic and Genetic Correlation in a Cohort of Chinese Patients with SYNE1 Variants Xiaohui Duan 1 & Ying Hao 1 & Zhenhua Cao 2 & Chao Zhou 2 & Jin Zhang 1 & Renbin Wang 1 & Shaojie Sun 1 & Weihong Gu 1 Accepted: 27 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene have been reported to cause autosomal recessive cerebellar ataxia (ARCA) type 1 with highly variable clinical phenotypes. The aim of this study was to describe the phenotypic-genetic spectrum of SYNE1-related ARCA1 patients in the Chinese population. We screened 158 unrelated patients with autosomal recessive or sporadic ataxia for variants in SYNE1 using next-generation sequencing. Pathogenicity assessment of SYNE1 variants was interpreted according to the American College of Medical Genetics standards and guidelines. We identified eight truncating variants and two missense variants spreading throughout the SYNE1 gene from six unrelated families, including nine novel variants and one reported variant. Of the six index patients, two patients showed the classical pure cerebellar ataxia, while four patients exhibited non-cerebellar phenotypes, including motor neuron symptoms, cognitive impairment, or mental retardation. The variants associated with motor neuron or cognition involvement tend to be located in the C-terminal region of SYNE1 protein, compared with the variants related to pure cerebellar ataxia. Our data indicating SYNE1 mutation is one of the more common causes of recessive ataxia in the Chinese population. The use of next-generation sequencing has enabled the rapid analysis of recessive ataxia and further expanded our understanding of genotype-phenotype correlation. Keywords Autosomal recessive cerebellar ataxia 1(ARCA1) . SYNE1 gene . Genotype . Phenotype . Whole-exome sequencing (WES)
Introduction The autosomal recessive cerebellar ataxias (ARCAs), also called spinocerebellar ataxias autosomal recessive (SCARs) are a group of complex neurodegenerative conditions with significant genetic and clinical heterogeneity [1]. They are usually characterized by early-onset ataxia with a variable range of other neurological manifestations such as pyramidal or extrapyramidal signs, cognitive deterioration, peripheral Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12311-020-01186-8) contains supplementary material, which is available to authorized users. * Weihong Gu [email protected] 1
Movement Disorder and Neurogenetics Research Center, Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, People’s Republic of China
2
Running Gene Inc, Beijing 100191, China
neuropathy, epilepsy, retinopathy, and endocrine manifestations. To date, the Society for Research on the Cerebellum and Ataxias Task Force identified 59 disorders that are classified as primary ARCAs, including 15 disorders that are more prevalent an
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