title: SNCA mutation p.Ala53Glu is derived from a common founder in the Finnish population.
abstract: Mutations in SNCA are rare causes of familial Parkinson's disease (PD). We have previously described a novel p.Ala53Glu mutation in 2 Finnish families. To assess this mutation's frequency among Finnish PD patients, we screened 110 PD patients (mean age-of-onset 60 years) from Western Finland by Sanger sequencing of the third coding exon of SNCA. In addition, a sample of 47 PD subjects (mean age-of-onset 53 years) originating from Southern and Eastern Finland were studied using next-generation sequencing covering SNCA. Only one new individual with the p.Ala53Glu mutation was identified, confirming that this mutation is a rare cause of PD in the Finnish population. To search for a possible common origin of the p.Ala53Glu mutation, haplotype analysis was conducted in 2 families and in a patient from a third family (6 affected subjects) using both STR markers and a genome-wide SNP array. The results show that patients with the p.Ala53Glu mutation share a haplotype spanning a minimum of 5.7 Mb suggesting a common founder.
authors.affiliation: Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland; Department of Medical Genetics, Tyks Microbiology and Genetics, Turku University Hospital, Turku, Finland.
authors.forename: Petra
authors.initials: P
authors.lastname: Pasanen
authors.affiliation: Molecular Neurology, Research Programs Unit, University of Helsinki, Helsinki, Finland.
authors.forename: Eino
authors.initials: E
authors.lastname: Palin
authors.affiliation: Molecular Neurology, Research Programs Unit, University of Helsinki, Helsinki, Finland.
authors.forename: Risto
authors.initials: R
authors.lastname: Pohjolan-Pirhonen
authors.affiliation: Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland; Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Pöyhönen
authors.affiliation: Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland; Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
authors.affiliation: Visby Lasarett, Visby, Sweden.
authors.forename: Markku
authors.initials: M
authors.lastname: Päivärinta
authors.affiliation: Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Mika H
authors.initials: MH
authors.lastname: Martikainen
authors.affiliation: Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland; Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland; Department of Neurology, University of Turku, Turku, Finland.
authors.forename: Valtteri
authors.initials: V
authors.lastname: Kaasinen
authors.affiliation: Department of Clinical Genetics, Turku University Hospital, Turku, Finland.
authors.forename: Marja
authors.initials: M
authors.lastname: Hietala
authors.affiliation: Department of Pathology, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Gardberg
authors.affiliation: Department of Neurology, North Karelia Central Hospital, Joensuu, Finland.
authors.forename: Anna Maija
authors.initials: AM
authors.lastname: Saukkonen
authors.affiliation: Molecular Neurology, Research Programs Unit, University of Helsinki, Helsinki, Finland; Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Eerola-Rautio
authors.affiliation: Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Kaakkola
authors.affiliation: Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Lyytinen
authors.affiliation: Molecular Neurology, Research Programs Unit, University of Helsinki, Helsinki, Finland; Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Pentti J
authors.initials: PJ
authors.lastname: Tienari
authors.affiliation: Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland.
authors.forename: Anders
authors.initials: A
authors.lastname: Paetau
authors.affiliation: Molecular Neurology, Research Programs Unit, University of Helsinki, Helsinki, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Suomalainen
authors.affiliation: Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland. Electronic address: liisa.myllykangas@helsinki.fi.
authors.forename: Liisa
authors.initials: L
authors.lastname: Myllykangas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005387:Finland; D018703:Founder Effect; D056726:Genetic Association Studies; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D044465:White People / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: A53E; Founder effect; Haplotype; SNCA