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.
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.
Authors: Bart P C van de Warrenburg; Paola Giunti; Susanne A Schneider; Niall P Quinn; Nicholas W Wood; Kailash P Bhatia Journal: J Neurol Neurosurg Psychiatry Date: 2006-12-08 Impact factor: 10.154
Authors: Esther A R Nibbeling; Cathérine C S Delnooz; Tom J de Koning; Richard J Sinke; Hyder A Jinnah; Marina A J Tijssen; Dineke S Verbeek Journal: Neurosci Biobehav Rev Date: 2017-01-28 Impact factor: 8.989
Authors: Sarah Doss; Jan Leo Rinnenthal; Tanja Schmitz-Hübsch; Alexander U Brandt; Sebastian Papazoglou; Silke Lux; Stephan Maul; Jens Würfel; Matthias Endres; Thomas Klockgether; Martina Minnerop; Friedemann Paul Journal: J Neurol Date: 2015-06-05 Impact factor: 4.849
Authors: Wiljan J A J Hendriks; Gönül Dilaver; Yvet E Noordman; Berry Kremer; Jack A M Fransen Journal: Cerebellum Date: 2009-01-10 Impact factor: 3.847