New mutations in protein kinase Cgamma associated with spinocerebellar ataxia type 14.
Ann Neurol.. 2005-01-01; 58(5): 720-729
DOI: 10.1002/ana.20628
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1. Ann Neurol. 2005 Nov;58(5):720-9.
New mutations in protein kinase Cgamma associated with spinocerebellar ataxia
type 14.
Klebe S(1), Durr A, Rentschler A, Hahn-Barma V, Abele M, Bouslam N, Schöls L,
Jedynak P, Forlani S, Denis E, Dussert C, Agid Y, Bauer P, Globas C, Wüllner U,
Brice A, Riess O, Stevanin G.
Author information:
(1)Institut National de la Sante et de la Recherche Médicale U679 (formerly U289)
and Institut Fédératif de Recherche en Neurosciences, Paris, France.
Autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of
neurological disorders. Point mutations in the gene encoding protein kinase
Cgamma (PRKCG) are responsible for spinocerebellar ataxia 14 (SCA14). We screened
for mutations in the PRKCG gene, in a large series of 284 ADCA index cases,
mostly French (n=204) and German (n=48), in whom CAG repeat expansions in the
known SCA genes were previously excluded. Six mutations were found that
segregated with the disease and were not detected on 560 control chromosomes,
including F643L (exon 18), already reported in another French kindred. Five new
missense mutations were identified in exons 4 (C114Y/G123R/G123E), 10 (G360S) and
18 (V692G). All but one (V692G) were located in highly conserved regions of the
regulatory or catalytic domains of the protein. All six SCA14 families were
French and there was no evidence of reduced penetrance. The phenotype consisted
in a very slowly progressive cerebellar ataxia with a mean age at onset of
33.5+/-14.2 years (range 15 to 60 years), occasionally associated with executive
dysfunction, myoclonus, myorythmia, tremor or decreased vibration sense. SCA14
represented only 1.5% (7/454) of French ADCA families but none of the German
families. It should, however, be considered in patients with slowly progressive
ADCA, particularly when myoclonus and cognitive impairment are present.
DOI: 10.1002/ana.20628
PMID: 16193476 [Indexed for MEDLINE]