title: FBXO7 mutations in Parkinson's disease and multiple system atrophy.
abstract: Mutations in the F-box only protein 7 (FBXO7) gene, located on chromosome 22q12-q13, have recently been identified as having distinct clinical features in patients with hereditary Parkinson's disease (PD). Pathologically, α-synuclein-positive inclusions have been identified using anti-FBXO7 antibody staining techniques. In the present study, we screened entire exons of FBXO7 from 271 patients (231 PD and 40 multiple system atrophy [MSA]), of which 221 samples were of Japanese origin. The PD patients (n = 231) comprised 31 autosomal dominant, 82 autosomal recessive, and 118 sporadic forms. The 40 cases of MSA consisted of 8 autosomal dominant, 2 autosomal recessive, and 30 sporadic forms. We detected a Turkish patient with autosomal recessive inheritance, harboring a homozygous truncating mutation, Arg498Stop (p.R498X), in the FBXO7 gene. Consequently, we evaluated her and assessed the correlation between her clinical manifestations and genotypic analysis, although the FBXO7 p.R498X gene has lower frequency than others. Her age at onset was 17 years, and she clinically manifested with progressive parkinsonism and cognitive decline. In contrast, no pathogenic mutations in FBXO7 among PD and MSA patients of Japanese or other ethnicities were observed. Based on recent literature, we reviewed and compared the clinical findings and population differences between documented FBXO7 cases.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Silvio
authors.initials: S
authors.lastname: Conedera
authors.affiliation: Cerrahpasa Medical Faculty, Department of Neurology, Istanbul University, Istanbul, Turkey.
authors.forename: Hulya
authors.initials: H
authors.lastname: Apaydin
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, 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: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsushima
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Funayama
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Nishioka
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan. Electronic address: nhattori@juntendo.ac.jp.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D044783:F-Box Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D056726:Genetic Association Studies; D006801:Humans; D007564:Japan / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000235:genetics*; D009154:Mutation; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D014421:Turkey / Q000208:ethnology; D055815:Young Adult; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D044783:F-Box Proteins; C489149:FBXO7 protein, human; D051844:alpha-Synuclein
keywords: FBXO7; Genetics; Multiple system atrophy; Parkinson's disease