title: Screening for VPS35 mutations in Parkinson's disease.
abstract: Recently 2 groups have independently identified a mutation in the gene 'vacuolar protein sorting 35 homolog' (VPS35 c.1858G>A; p.Asp620Asn) as a possible cause of autosomal dominant Parkinson's disease (PD). In order to assess the frequency of the reported mutation and to search for other possible disease-causing variants in this gene, we sequenced all 17 exons of VPS35 in 96 familial PD cases, and exon 15 (in which the reported mutation is found) in an additional 64 familial PD cases, 175 young-onset PD cases, and 262 sporadic, neuropathologically confirmed PD cases. We identified 1 individual with the p.Asp620Asn mutation and an autosomal dominant family history of PD. Subsequent follow-up of the family confirmed an affected sibling and cousin who also carried the same mutation. No other potentially disease-causing mutations were identified. We conclude that the VPS35 c.1858G>A mutation is an uncommon cause of familial Parkinson's disease in our population.
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Una-Marie
authors.initials: UM
authors.lastname: Sheerin
authors.forename: Gavin
authors.initials: G
authors.lastname: Charlesworth
authors.forename: Jose
authors.initials: J
authors.lastname: Bras
authors.forename: Rita
authors.initials: R
authors.lastname: Guerreiro
authors.forename: Kailash
authors.initials: K
authors.lastname: Bhatia
authors.forename: Thomas
authors.initials: T
authors.lastname: Foltynie
authors.forename: Patricia
authors.initials: P
authors.lastname: Limousin
authors.forename: Laura
authors.initials: L
authors.lastname: Silveira-Moriyama
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wood
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins