Identification of a novel mutation in the CACNA1C gene in a Chinese family with autosomal dominant cerebellar ataxia

Jiajun Chen,Yajuan Sun,Xiaoyang Liu,Jia Li

doi:10.1186/s12883-019-1381-8

Jiajun Chen, Yajuan Sun + Show 2 more

Open Access

https://doi.org/10.1186/s12883-019-1381-8

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Journal: BMC Neurology	Publication Date: Jul 10, 2019
Citations: 6	License type: open-access

Affiliation: Union Hospital, Jilin University

Abstract

BackgroundHereditary ataxia is a group of neurodegenerative diseases with progressive cerebellar ataxia of the gait and limbs as the main symptoms. The genetic patterns of the disease are diverse but it is mainly divided into autosomal dominant cerebellar ataxia (ADCA) and autosomal recessive cerebellar ataxia (ARCA), and about 45 pathogenic loci have been found in ADCA. The purpose of this study was to explore the genetic defect in a Chinese family with ADCA.MethodsA three-generation Chinese family with ADCA was enrolled in this study, Exome sequencing was conducted in four family members, including the proband, and verified by Sanger sequencing.ResultsThe rs779393130 mutation of the CACNA1C gene co-segregated with the ataxia phenotype in this family. The mutation was not detected in 50 unaffected controls.ConclusionsThe rs779393130 mutation of CACNA1C may be associated with the phenotype of the disease. The CACNA1C gene encodes the Cav1.2 (alpha-1) subunit of an L-type calcium channel and this subunit may be related to the ADCA phenotype. These findings may have implications for family clinical monitoring and genetic counseling and may also help in understanding pathogenesis of this disease.

Highlights

Hereditary ataxia is a group of neurodegenerative diseases with progressive cerebellar ataxia of the gait and limbs as the main symptoms
About 45 pathogenic loci have been found in autosomal dominant cerebellar ataxia (ADCA), 35 of which have been cloned, and 70 pathogenic loci have been found in autosomal recessive cerebellar ataxia (ARCA), at least 50 of which have been cloned [4]
Consistent with reports that mutations in channel-encoding genes may cause ADCA, we proposed that a novel mutation in calcium voltage-gated channel subunit alpha1 C (CACNA1C) may be related to ADCA in this family

Summary

Introduction

Hereditary ataxia is a group of neurodegenerative diseases with progressive cerebellar ataxia of the gait and limbs as the main symptoms. Hereditary ataxia (HA) is a group of neurodegenerative diseases with progressive cerebellar ataxia of the gait and limbs as the main symptoms; HA affects the cerebellum, brainstem, spinal cord, and cranial nerve nuclei [1]. It is a highly genetically and clinically heterogeneous disease that accounts for about 10 to 15% of nervous system genetic disorders.

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