Clinical phenotypes study of autosomal recessive cerebellar ataxia type 1 caused by SYNE 1 gene mutations
10.3760/cma.j.issn.1006-7876.2019.10.002
- VernacularTitle: SYNE 1基因突变致常染色体隐性遗传小脑共济失调1型表型分析
- Author:
Xiaohui DUAN
1
;
Ying HAO
;
Weihong GU
;
Jin ZHANG
Author Information
1. Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China
- Publication Type:Journal Article
- Keywords:
Cerebellar ataxia;
SYNE 1 gene;
Cerebellar atrophy;
Mutation;
Phenotype
- From:
Chinese Journal of Neurology
2019;52(10):797-805
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical features of autosomal recessive cerebellar ataxia type 1 (ARCA1) and analyze the pathogenic variants in SYNE 1 gene.
Methods:A cohort of 80 probands of autosomal recessive cerebellar ataxia pedigrees excluding Friedreich ataxia were detected by whole-exome sequencing technology. Potential pathogenic variants were confirmed by Sanger sequencing. Clinical phenotypes of positive patients were analyzed in detail.
Results:Three pedigrees of ARCA1 caused by SYNE 1 gene variants were found. The proband of pedigree 1 carried homozygous frameshift mutation c.12670dupC(p.L4224fs), presented as pure cerebellar ataxia. The proband of pedigree 2 carried compound heterozygous mutations c.20826+1G>T and c.25954C>T(p.R8652X), presented as cerebellar ataxia plus upper motor neuron dysfunction. The proband of pedigree 3 carried compound heterozygous mutations c.21955C>T(p.Q7319X) and c.23777C>A(p.T7926K), presented as mental behavior and cognitive impairment, cerebellar ataxia and upper motor neuron dysfunction. Brain MRI showed obvious cerebellar atrophy in all patients, and the fronto-temporal lobes were also found slight atrophy in proband of pedigree 3.
Conclusions:The phenotype of ARCA1 caused by SYNE 1 gene mutations is characterized by cerebellar ataxia, maybe accompanied with motor neuron damage and cognitive dysfunction. ARCA1 is a rare form of autosomal recessive cerebellar ataxia in Chinese population, with a complex phenotype. The use of next generation sequencing allows the rapid analysis of ARCA1, and will likely further expand genotype-phenotype correlations.
