title: Mutation screening of PLA2G6 in Japanese patients with early onset dystonia-parkinsonism.
abstract: A recessive mutation in PLA2G6, which is known to cause infantile neuroaxonal dystrophy (INAD) and neurodegeneration associated with brain iron accumulation (NBIA), has recently been shown to be responsible for PARK14-linked dystonia-parkinsonism. To study the frequency of PLA2G6 mutations, including those caused by gene rearrangement in patients with parkinsonism, we performed direct sequencing and investigated copy number variations (CNVs) of this gene in 109 Japanese patients with parkinsonism. Direct sequencing revealed a homozygous mutation (c.1495G>A; p.A499T), which is likely to be pathogenic and is already registered as rs141045127, and two compound-heterozygous mutations we have previously reported. No CNVs in PLA2G6 were detected in our subjects. Our results suggest that CNV in PLA2G6 is rare in parkinsonism, at least in the Japanese population, in contrast to the reports of its frequency in INAD. Further large studies in various populations are warranted to elucidate what causes the difference in frequencies of PLA2G6 rearrangement mutations between INAD and dystonia-parkinsonism.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 3-3-11 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Yamashita
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 3-3-11 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.|Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Funayama
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 3-3-11 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Yuanzhe
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Yoshino
authors.affiliation: Yokohama Neurology Clinic, Kanagawa, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Neurology, Hirosaki Municipal Hospital, Aomori, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Seino
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 3-3-11 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomiyama
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 3-3-11 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. nhattori@juntendo.ac.jp.|Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan. nhattori@juntendo.ac.jp.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
keywords: Copy number variation (CNV); PARK14; PLA2G6; Parkinsonism