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

Abstract Background: Hereditary 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. Methods: A 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. Results: The rs779393130 mutation of the CACNA1C gene co-segregated with the ataxia phenotype in this family. The mutation was not detected in 50 unaffected controls. Conclusions: The 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.

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

10.21203/rs.2.9243/v1 ◽

2019 ◽

Author(s):

Jiajun Chen ◽

Yajuan Sun ◽

Xiaoyang Liu ◽

Jia Li

Keyword(s):

Cerebellar Ataxia ◽

Autosomal Recessive ◽

Autosomal Dominant ◽

Novel Mutation ◽

Genetic Defect ◽

Autosomal Dominant Cerebellar Ataxia ◽

Chinese Family ◽

Autosomal Recessive Cerebellar Ataxia ◽

Progressive Cerebellar Ataxia ◽

Genetic Patterns

Abstract Background: Hereditary 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. Methods: A 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. Results: The rs779393130 mutation of the CACNA1C gene co-segregated with the ataxia phenotype in this family. The mutation was not detected in 50 unaffected controls. Conclusions: The 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.

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

10.21203/rs.2.9243/v2 ◽

2019 ◽

Author(s):

Jiajun Chen ◽

Yajuan Sun ◽

Xiaoyang Liu ◽

Jia Li

Keyword(s):

Cerebellar Ataxia ◽

Autosomal Recessive ◽

Autosomal Dominant ◽

Novel Mutation ◽

Genetic Defect ◽

Autosomal Dominant Cerebellar Ataxia ◽

Chinese Family ◽

Autosomal Recessive Cerebellar Ataxia ◽

Progressive Cerebellar Ataxia ◽

Genetic Patterns

Abstract Background: Hereditary 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. Methods: A 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. Results: The rs779393130 mutation of the CACNA1C gene co-segregated with the ataxia phenotype in this family. The mutation was not detected in 50 unaffected controls. Conclusions: The 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.

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

10.21203/rs.2.9243/v4 ◽

2019 ◽

Author(s):

Jiajun Chen ◽

Yajuan Sun ◽

Xiaoyang Liu ◽

Jia Li

Keyword(s):

Cerebellar Ataxia ◽

Autosomal Recessive ◽

Autosomal Dominant ◽

Novel Mutation ◽

Genetic Defect ◽

Autosomal Dominant Cerebellar Ataxia ◽

Chinese Family ◽

Autosomal Recessive Cerebellar Ataxia ◽

Progressive Cerebellar Ataxia ◽

Genetic Patterns

Abstract Background: Hereditary 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. Methods: A 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. Results: The rs779393130 mutation of the CACNA1C gene co-segregated with the ataxia phenotype in this family. The mutation was not detected in 50 unaffected controls. Conclusions: The 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.

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DNMT1-complex disorder caused by a novel mutation associated with an overlapping phenotype of autosomal-dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) and hereditary sensory neuropathy with dementia and hearing loss (HSN1E)

Neurological Sciences ◽

10.1007/s10072-019-03859-7 ◽

2019 ◽

Vol 40 (9) ◽

pp. 1963-1966 ◽

Cited By ~ 1

Author(s):

Alessia Catania ◽

Lorenzo Peverelli ◽

Silvia Tabano ◽

Daniele Ghezzi ◽

Costanza Lamperti

Keyword(s):

Hearing Loss ◽

Cerebellar Ataxia ◽

Autosomal Dominant ◽

Novel Mutation ◽

Sensory Neuropathy ◽

Autosomal Dominant Cerebellar Ataxia ◽

Complex Disorder ◽

Hereditary Sensory Neuropathy

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SCA14 in Norway, two families with autosomal dominant cerebellar ataxia and a novel mutation in the PRKCG gene

Acta Neurologica Scandinavica ◽

10.1111/j.1600-0404.2011.01504.x ◽

2011 ◽

Vol 125 (2) ◽

pp. 116-122 ◽

Cited By ~ 9

Author(s):

J. Koht ◽

G. Stevanin ◽

A. Durr ◽

E. Mundwiller ◽

A. Brice ◽

...

Keyword(s):

Cerebellar Ataxia ◽

Autosomal Dominant ◽

Novel Mutation ◽

Autosomal Dominant Cerebellar Ataxia

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Spinocerebellar ataxia type 28: A novel autosomal dominant cerebellar ataxia characterized by slow progression and ophthalmoparesis

The Cerebellum ◽

10.1007/s12311-008-0053-9 ◽

2008 ◽

Vol 7 (2) ◽

pp. 184-188 ◽

Cited By ~ 42

Author(s):

Caterina Mariotti ◽

Alfredo Brusco ◽

Daniela Di Bella ◽

Claudia Cagnoli ◽

Marco Seri ◽

...

Keyword(s):

Cerebellar Ataxia ◽

Spinocerebellar Ataxia ◽

Autosomal Dominant ◽

Autosomal Dominant Cerebellar Ataxia ◽

Spinocerebellar Ataxia Type ◽

Slow Progression

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Phenotypic variability in autosomal dominant cerebellar ataxia type I is unrelated to genetic heterogeneity

Brain ◽

10.1093/brain/116.6.1497 ◽

1993 ◽

Vol 116 (6) ◽

pp. 1497-1508 ◽

Cited By ~ 26

Author(s):

A. Durr ◽

H. Chneiweiss ◽

C. Khati ◽

G. Stevanin ◽

G. Cancel ◽

...

Keyword(s):

Cerebellar Ataxia ◽

Genetic Heterogeneity ◽

Autosomal Dominant ◽

Phenotypic Variability ◽

Autosomal Dominant Cerebellar Ataxia ◽

Type I

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A Novel COMP Mutated Allele Identified in a Chinese Family with Pseudoachondroplasia

BioMed Research International ◽

10.1155/2021/6678531 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Bing-Bing Guo ◽

Jie-Yuan Jin ◽

Zhuang-Zhuang Yuan ◽

Lei Zeng ◽

Rong Xiang

Keyword(s):

Extracellular Matrix ◽

Cartilage Oligomeric Matrix Protein ◽

Matrix Protein ◽

Autosomal Dominant ◽

Novel Mutation ◽

Chinese Family ◽

The Novel ◽

Structure Model ◽

Whole Exome ◽

Nucleotide Mutation

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia with an estimated incidence of ~1/60000 that is characterized by disproportionate short stature, brachydactyly, joint laxity, and early-onset osteoarthritis. COMP encodes the cartilage oligomeric matrix protein, which is expressed predominantly in the extracellular matrix (ECM) surrounding the cells that make up cartilage, ligaments, and tendons. Mutations in COMP are known to give rise to PSACH. In this study, we identified a novel nucleotide mutation (NM_000095.2: c.1317C>G, p.D439E) in COMP responsible for PSACH in a Chinese family by employing whole-exome sequencing (WES) and built the structure model of the mutant protein to clarify its pathogenicity. The novel mutation cosegregated with the affected individuals. Our study expands the spectrum of COMP mutations and further provides additional genetic testing information for other PSACH patients.

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