title: New mutations in protein kinase Cgamma associated with spinocerebellar ataxia type 14.
abstract: 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.
authors.affiliation: Institut National de la Sante et de la Recherche Médicale U679 (formerly U289) and Institut Fédératif de Recherche en Neurosciences, Paris, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Klebe
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Alexander
authors.initials: A
authors.lastname: Rentschler
authors.forename: Valerie
authors.initials: V
authors.lastname: Hahn-Barma
authors.forename: Michael
authors.initials: M
authors.lastname: Abele
authors.forename: Naima
authors.initials: N
authors.lastname: Bouslam
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
authors.forename: Pierre
authors.initials: P
authors.lastname: Jedynak
authors.forename: Sylvie
authors.initials: S
authors.lastname: Forlani
authors.forename: Elodie
authors.initials: E
authors.lastname: Denis
authors.forename: Christel
authors.initials: C
authors.lastname: Dussert
authors.forename: Yves
authors.initials: Y
authors.lastname: Agid
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Christoph
authors.initials: C
authors.lastname: Globas
authors.forename: Ullrich
authors.initials: U
authors.lastname: Wüllner
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004576:Electromyography / Q000379:methods; D005091:Exons; D005192:Family Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D011493:Protein Kinase C / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: C087857:protein kinase C gamma; D011493:Protein Kinase C