title: Identification of a new family of spinocerebellar ataxia type 14 in the Japanese spinocerebellar ataxia population by the screening of PRKCG exon 4.
abstract: Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia and intermittent axial myoclonus. Various mutations have been found in the PRKCG gene encoding protein kinase C gamma in SCA14 families. Most of those mutations have been found in exon 4 of the PRKCG gene. We performed polymerase chain reaction (PCR)-based screening to clarify the approximate morbidity rate of the disease in the Japanese SCA population. We screened exon 4 of the PRKCG gene in 882 SCA patients with undefined etiologies using denaturing high-performance liquid chromatography and subsequent direct sequencing. We found a novel C/T missense mutation with a Ser119-to-Phe substitution (S119F) in 2 patients and subsequently found that they belonged to the same family. This S119F mutation was not found in 259 control individuals. Further PCR-based analysis revealed an additional 5 members with the same mutation in this family. Cerebellar ataxia was manifested in 5 of those 7 members. The main symptom in 4 of the 5 affected members was pure cerebellar ataxia with late onset. They had no myoclonus, extrapyramidal signs, ophthalmoplegia, or intellectual disturbance, some of which were found in previously reported SCA families. One patient showed intractable epilepsy, severe walking disturbance, and trunk ataxia with early onset. The results of this study suggest that the frequency of SCA14 in the Japanese SCA population is very low.
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Hiramoto
authors.forename: Hideshi
authors.initials: H
authors.lastname: Kawakami
authors.forename: Kimiko
authors.initials: K
authors.lastname: Inoue
authors.forename: Takahiro
authors.initials: T
authors.lastname: Seki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Maruyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morino
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kurisu
authors.forename: Norio
authors.initials: N
authors.lastname: Sakai
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007438:Introns; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010649:Phenylalanine / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics*; D012694:Serine / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000235:genetics*
chemical_list: D012694:Serine; D010649:Phenylalanine; C087857:protein kinase C gamma; D011493:Protein Kinase C