Dataset Information

A novel frameshift mutation of SYNE1 in a Japanese family with autosomal recessive cerebellar ataxia type 8.

ABSTRACT: A Japanese family with autosomal recessive cerebellar ataxia type 8 (SCAR8, MIM 610743) is described. We identified a novel SYNE1 frameshift deletion (c.6843del, p.Q2282Sfs*3). This family shared similar clinical manifestations characterized by adult-onset, relatively pure cerebellar ataxia with mild eye movement abnormality. Intelligence and bulbar and respiratory functions were unaffected. This study suggests the clinical utility of using panel-based exome sequencing for genetic diagnosis in hereditary ataxias in a cost-efficient manner.

SUBMITTER: Yoshinaga T

PROVIDER: S-EPMC5656760 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

A novel frameshift mutation of <i>SYNE1</i> in a Japanese family with autosomal recessive cerebellar ataxia type 8.

Yoshinaga Tsuneaki T Nakamura Katsuya K Ishikawa Masumi M Yamaguchi Tomomi T Takano Kyoko K Wakui Keiko K Kosho Tomoki T Yoshida Kunihiro K Fukushima Yoshimitsu Y Sekijima Yoshiki Y

Human genome variation 20171026

A Japanese family with autosomal recessive cerebellar ataxia type 8 (SCAR8, MIM 610743) is described. We identified a novel <i>SYNE1</i> frameshift deletion (c.6843del, p.Q2282Sfs*3). This family shared similar clinical manifestations characterized by adult-onset, relatively pure cerebellar ataxia with mild eye movement abnormality. Intelligence and bulbar and respiratory functions were unaffected. This study suggests the clinical utility of using panel-based exome sequencing for genetic diagnos ...[more]

PMID: 29081981

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Project description:Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene have been reported to cause a relatively pure, slowly progressive cerebellar recessive ataxia mostly identified in Quebec, Canada. Combining next-generation sequencing techniques and deep-phenotyping (clinics, magnetic resonance imaging, positron emission tomography, muscle histology), we here established the frequency, phenotypic spectrum and genetic spectrum of SYNE1 in a screening of 434 non-Canadian index patients from seven centres across Europe. Patients were screened by whole-exome sequencing or targeted panel sequencing, yielding 23 unrelated families with recessive truncating SYNE1 mutations (23/434 = 5.3%). In these families, 35 different mutations were identified, 34 of them not previously linked to human disease. While only 5/26 patients (19%) showed the classical SYNE1 phenotype of mildly progressive pure cerebellar ataxia, 21/26 (81%) exhibited additional complicating features, including motor neuron features in 15/26 (58%). In three patients, respiratory dysfunction was part of an early-onset multisystemic neuromuscular phenotype with mental retardation, leading to premature death at age 36 years in one of them. Positron emission tomography imaging confirmed hypometabolism in extra-cerebellar regions such as the brainstem. Muscle biopsy reliably showed severely reduced or absent SYNE1 staining, indicating its potential use as a non-genetic indicator for underlying SYNE1 mutations. Our findings, which present the largest systematic series of SYNE1 patients and mutations outside Canada, revise the view that SYNE1 ataxia causes mainly a relatively pure cerebellar recessive ataxia and that it is largely limited to Quebec. Instead, complex phenotypes with a wide range of extra-cerebellar neurological and non-neurological dysfunctions are frequent, including in particular motor neuron and brainstem dysfunction. The disease course in this multisystemic neurodegenerative disease can be fatal, including premature death due to respiratory dysfunction. With a relative frequency of ∼5%, SYNE1 is one of the more common recessive ataxias worldwide.

Dataset Information

A novel frameshift mutation of SYNE1 in a Japanese family with autosomal recessive cerebellar ataxia type 8.

Publications

A novel frameshift mutation of <i>SYNE1</i> in a Japanese family with autosomal recessive cerebellar ataxia type 8.

Similar Datasets

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