講演情報
[P12-8]パーキンソン病におけるPRKN変異の臨床遺伝学的検討
○吉野 浩代1, 李 元哲2, 西岡 健弥2, 代田 健祐2, 林田 有紗2, 石黒 雄太2, 山田 大介2, 伊澤 奈々2, 西 克典2, 西川 典子2, 大山 彦光2, 波田野 琢2, 中村 真一郎3, 頼高 朝子4, 本井 ゆみ子2, 舩山 学1,2,5, 服部 信孝1,2,5,6 (1.順天堂大学大学院 医学研究科 老人性疾患病態・治療研究センター, 2.順天堂大学 脳神経内科, 3.越谷市立病院 神経内科, 4.順天堂越谷病院 脳神経内科, 5.順天堂大学大学院 医学研究科 ゲノム・再生医療センター, 6.理化学研究所 脳神経科学研究センター 神経変性疾患連携研究チーム)
【Objective】The parkin RBR E3 ubiquitin protein ligase (PRKN) was identified as a causal gene for young-onset Parkinson’s disease (PD) with autosomal recessive form. Parkin collaborated PINK1 maintains mitochondrial functions, thus the loss of function of parkin is profoundly related to pathomechanism of young-onset familial PD. We aimed to elucidate the prevalence and genotype-phenotype correlations of PRKN variants in PD.【Methods】We screened PRKN variants by Sanger sequencing or gene panel sequencing using Ion Torrent system in 2,322 Japanese patients including 1,204 with familial and 1,118 with sporadic PD. The copy number variants (CNVs) of PRKN were analyzed using the multiplex ligation-dependent probe amplification methods. We divided patients harboring PRKN variants into two groups: patients with monoallelic variant (mono-allele) and with biallelic variants (bi-allele), and compared clinical features between the two groups.【Results】We identified 242 patients harboring PRKN variants comprising 57 patients with mono-allele, 163 with bi-allele, and 22 with contiguous exon heterozygous CNVs not categorized in either group, the prevalence of PRKN variants carriers was 10.4% in our cohort. The patients with bi-allele were significantly younger at onset than those with mono-allele. There were significant differences in the rate of some symptoms or the frequencies of normal values of 123I-MIBG myocardial scintigraphy between the two groups. 【Conclusions】The patients with PRKN variants showed specific symptoms dependent on the number of mutated alleles.