Progressive ataxia caused by mutation of CACNA1A (c.3451G > A): a case report

Abstract Background Progressive cerebellar ataxia is a genetically heterogeneous neurological disorder. While mutations in the CACNA1A gene are known to cause various spinocerebellar ataxias, reports of specific point mutations leading to the disease in the Chinese population remain limited. This study describes a novel CACNA1A mutation identified in a Chinese family with autosomal dominant progressive cerebellar ataxia. Case presentation A 58-year-old male proband presented with symptoms of progressive cerebellar ataxia. Genetic analyses, including PCR, capillary gel electrophoresis, high throughput sequencing, and subsequent first-generation sequencing, were performed. The results identified a heterozygous mutation in CACNA1A (c.3451G > A), which was not associated with CAG trinucleotide repeat expansions. Familial co-segregation analysis revealed that his affected sister also carried the identical mutation, supporting its pathogenic role in the family. Furthermore, cross-species sequence alignment using DNAMAN demonstrated that the c.3451 locus is highly evolutionarily conserved. Conclusion We report the first Chinese pedigree with progressive cerebellar ataxia caused by a heterozygous CACNA1A (c.3451G > A) mutation. The high conservation of this locus suggests its critical functional importance, and the mutation is predicted to result in an amino acid subs titution that disrupts protein function. Our findings expand the genetic spectrum of CACNA1A -related disorders and provide valuable clinical and molecular insights into the etiology of progressive ataxia.