Identification of a New Family of Spinocerebellar Ataxia Type 14 in the Japanese Spinocerebellar Ataxia Population by the Screening of PRKCG Exon 4 Keiko Hiramoto, MD, PhD, 1,2 Hideshi Kawakami, MD, PhD, 3 * Kimiko Inoue, MD, 4 Takahiro Seki, PhD, 2 Hirofumi Maruyama, MD, PhD, 3 Hiroyuki Morino, MD, PhD, 3 Masayasu Matsumoto, MD, PhD, 3 Kaoru Kurisu, MD, PhD, 1 and Norio Sakai, MD, PhD 2 1 Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan 2 Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan 3 Department of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan 4 Department of Neurology, Hyogo Rehabilitation Center Hospital, Nishi-ku, Kobe, Japan Abstract: Spinocerebellar ataxia type 14 (SCA14) is an auto- somal dominant neurodegenerative disorder characterized by cerebellar ataxia and intermittent axial myoclonus. Various mutations have been found in the PRKCG gene encoding protein kinase C  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 subse- quently 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, ophthal- moplegia, 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. © 2006 Movement Disorder Society Key words: protein kinase C; spinocerebellar ataxia; point mutation Autosomal dominant spinocerebellar ataxias (SCAs) are classified on the basis of susceptible gene loci. Twen- ty-five autosomal dominant ataxias have been identified to date. In most cases of SCA, nucleotide repeat expan- sions were identified in responsible genes. Six SCA subtypes (SCA1, SCA2, Machado–Joseph Disease [MJD], SCA6, SCA7, and SCA17) and dentatorubral– pallidoluysian atrophy (DRPLA) are caused by CAG trinucleotide repeat expansions in the coding region of respective genes. 1 Nucleotide repeat expansions were also found in the 5' untranslated and promoter region (SCA12), 2 intron (SCA10), 3 and 3' noncoding region (SCA8) 4 of responsible genes. Three autosomal dominant SCAs were found to be caused by point mutations, not by nucleotide repeat expansion. 5–7 Among them, SCA14 was caused by mis- sense mutations that were identified in the PRKCG gene encoding  subtype of protein kinase C (PKC). 6 SCA14, the locus of which is located in chromosome 19q, was first described in a 4-generation Japanese fam- *Correspondence to: Dr. Hideshi Kawakami, Department of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical Sci- ences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail: hkawakam@hiroshima-u.ac.jp Received 4 July 2005; Revised 29 November 2005; Accepted 18 January 2006 Published online 8 June 2006 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20970 Movement Disorders Vol. 21, No. 9, 2006, pp. 1355–1360 © 2006 Movement Disorder Society 1355