title: VPS35 mutation in Japanese patients with typical Parkinson's disease.
abstract: Vacuolar protein sorting 35 (VPS35) was recently reported to be a pathogenic gene for late-onset autosomal dominant Parkinson's disease (PD), using exome sequencing. To date, VPS35 mutations have been detected only in whites with PD. The aim of the present study was to determine the incidence and clinical features of Asian PD patients with VPS35 mutations. We screened 7 reported nonsynonymous missense variants of VPS35, including p.D620N, known as potentially disease-associated variants of PD, in 300 Japanese index patients with autosomal dominant PD and 433 patients with sporadic PD (SPD) by direct sequencing or high-resolution melting (HRM) analysis. In addition, we screened 579 controls for the p.D620N mutation by HRM analysis. The p.D620N mutation was detected in 3 patients with autosomal dominant PD (1.0%), in 1 patient with SPD (0.23%), and in no controls. None of the other reported variants of VPS35 were detected. Haplotype analysis suggested at least 3 independent founders for Japanese patients with p.D620N mutation. Patients with the VPS35 mutation showed typical tremor-predominant PD. We report Asian PD patients with the VPS35 mutation. Although VPS35 mutations are uncommon in PD, the frequency of such mutation is relatively higher in Japanese than reported in other populations. In VPS35, p.D620N substitution may be a mutational hot spot across different ethnic populations. Based on the clinical features, VPS35 should be analyzed in patients with PD, especially autosomal dominant PD or tremor-predominant PD.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Ando
authors.forename: Manabu
authors.initials: M
authors.lastname: Funayama
authors.forename: Yuanzhe
authors.initials: Y
authors.lastname: Li
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kashihara
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Murakami
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ishizu
authors.forename: Chizuko
authors.initials: C
authors.lastname: Toyoda
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Noguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakano
authors.forename: Ryogen
authors.initials: R
authors.lastname: Sasaki
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Kokubo
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kuzuhara
authors.forename: Kotaro
authors.initials: K
authors.lastname: Ogaki
authors.forename: Chikara
authors.initials: C
authors.lastname: Yamashita
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Yoshino
authors.forename: Taku
authors.initials: T
authors.lastname: Hatano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomiyama
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D002648:Child; D004185:Disability Evaluation; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins; D001224:Aspartic Acid; D001216:Asparagine