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.


CONCLUSIONS
A SCA-14-linked Dutch ADCA family with a novel missense mutation in the PRKCG gene was identified.
van de Warrenburg
B P C
BP
Department of Neurology, University Medical Center Nijmegen, the Netherlands.
Verbeek
D S
DS
Piersma
S J
SJ
Hennekam
F A M
FA
Pearson
P L
PL
Knoers
N V A M
NV
Kremer
H P H
HP
Sinke
R J
RJ
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002524:Cerebellar Ataxia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009426:Netherlands / Q000453:epidemiology; D010375:Pedigree; D011493:Protein Kinase C / Q000235:genetics*
C087857:protein kinase C gamma; D011493:Protein Kinase C