期刊
HUMAN HEREDITY
卷 -, 期 -, 页码 -出版社
KARGER
DOI: 10.1159/000534692
关键词
Spinocerebellar ataxia; CCDC88C; Whole-exome sequencing; Sanger sequencing; minigene assay; SCA40
In this study, a novel pathogenic mutation in the CCDC88C gene was identified as the cause of autosomal dominant Spinocerebellar ataxia (SCA) in a Chinese kindred. This mutation leads to SCA40, a rare subtype of SCA, and is associated with a later-onset phenotype. These findings contribute to the understanding of the genetic basis of SCA40 and provide important information for genetic counseling.
Introduction: Spinocerebellar ataxia (SCA) is an autosomal dominant genetic disease characterized by cerebellar neurological deficits. Specifically, its primary clinical manifestation is ataxia accompanied by peripheral nerve damage. A total of 48 causative genes of SCA have been identified. This study aimed to identify causative genes of autosomal dominant SCA in a four-generation Chinese kindred comprised of eight affected individuals. Methods: Genomic DNA samples were extracted from the pedigree members, and genomic whole-exome sequencing (WES) was performed, followed by bidirectional Sanger sequencing, and minigene assays to identify mutation sites. Results: A novel pathogenic heterozygous mutation in the splice region of the coiled-coil domain containing the 88C (CCDC88C) gene (NM_001080414:c.3636-4 A>G) was identified in four affected members. The minigene assay results indicated that this mutation leads to the insertion of CAG bases (c.3636-1_3636-3 insCAG). Conclusion: CCDC88C gene mutation leads to SCA40 (OMIM:616053), which is a rare subtype of SCA without symptoms during childhood. Our findings further demonstrated the role of the CCDC88C gene in SCA and indicated that the c.3636-4 A>G (NM_001080414) variant of CCDC88C is causative for a later-onset phenotype of SCA40. Our findings enrich the mutation spectrum of CCDC88C gene and provide a theoretical basis for the genetic counseling of SCA40.
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