Identification of a novel SCA14 mutation in a Dutch autosomal dominant cerebellar ataxia family

Objective: To report a Dutch family with autosomal dominant cerebellar ataxia (ADCA) based on a novel mutation in the PRKCG gene. Methods: The authors studied 13 affected members of the six-generation family. After excluding the known spinocerebellar ataxia (SCA) genes, a combination of the shared haplotype approach, linkage analysis, and genealogic investigations was used. Exons 4 and 5 of the candidate gene, PRKCG, were sequenced. Results: Affected subjects displayed a relatively uncomplicated, slowly progressive cerebellar syndrome, with a mean age at onset of 40.8 years. A focal dystonia in two subjects with an onset of disease in their early 20s suggests extrapyramidal features in early onset disease. Significant linkage to a locus on chromosome 19q was found, overlapping the SCA-14 region. Based on the recent description of three missense mutations in the PRKCG gene, located within the boundaries of the SCA-14 locus, we sequenced exons 4 and 5 of this gene and detected a novel missense mutation in exon 4, which involves a G→A transition in nucleotide 353 and results in a glycine-to-aspartic acid substitution at residue 118. Conclusion: A SCA-14-linked Dutch ADCA family with a novel missense mutation in the PRKCG gene was identified.