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

B. P.C. Van De Warrenburg, D. S. Verbeek, S. J. Piersma, F. A.M. Hennekam, P. L. Pearson, N. V.A.M. Knoers, H. P.H. Kremer, R. J. Sinke

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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.

Original languageEnglish
Pages (from-to)1760-1765
Number of pages6
Issue number12
StatePublished - Dec 23 2003


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