A Novel c.3636-4 A&gt;G Mutation in the <i>CCDC88C</i> Plays a Causative Role in Familial Spinocerebellar Ataxia

Abstract

<b><i>Introduction:</i></b> 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 comprising eight affected individuals. <b><i>Methods:</i></b> Genomic DNA samples were extracted from the pedigree members, and genomic whole-exome sequencing was performed, followed by bidirectional Sanger sequencing, and minigene assays to identify mutation sites. <b><i>Results:</i></b> A novel pathogenic heterozygous mutation in the splice region of the coiled-coil domain containing the 88C (<i>CCDC88C</i>) gene (NM_001080414:c.3636-4 A&gt;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). <b><i>Conclusion:</i></b> <i>CCDC88C</i> 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 <i>CCDC88C</i> gene in SCA and indicated that the c.3636-4 A&gt;G (NM_001080414) variant of <i>CCDC88C</i> is causative for a later-onset phenotype of SCA40. Our findings enrich the mutation spectrum of <i>CCDC88C</i> gene and provide a theoretical basis for the genetic counseling of SCA40.