NEUROLOGY 2003;61:1760-1765
© 2003 American Academy of Neurology
Identification of a novel SCA14 mutation in a Dutch autosomal dominant cerebellar ataxia family
B. P.C. van de Warrenburg, MD*,
D. S. Verbeek, MSc*,
S. J. Piersma, MSc,
F. A.M. Hennekam, MA,
P. L. Pearson, MD PhD,
N. V.A.M. Knoers, MD PhD,
H. P.H. Kremer, MD PhD and
R. J. Sinke, PhD
From the Departments of Neurology (Drs. van de Warrenburg and Kremer) and Human Genetics (Dr. Knoers), University Medical Center Nijmegen; and Department of Medical Genetics (D.S. Verbeek, S.J. Piersma, and F.A.M. Hennekam, and Drs. Pearson and Sinke), University Medical Center Utrecht, the Netherlands.
Address correspondence and reprint requests to D.S. Verbeek, Department of Medical Genetics, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands; e-mail: D.S.Verbeek{at}med.uu.nl
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.
Received May 5, 2003.
Accepted in final form August 20, 2003.
*Both authors contributed equally.
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