title: Genealogical studies in LRRK2-associated Parkinson's disease in central Norway.
abstract: The most common mutation related to Parkinson's disease (PD) is the p.G2019S mutation in the LRRK2 gene. Global population frequencies and crude estimates of haplotype conservation suggest most carriers are related. A total of 671 Norwegian PD patients and 215 of their family members were screened for the LRRK2 p.G2019S mutation. Twenty-one PD cases and 44 family members were positive for the mutation and all could be traced back to 10 different families. A genealogical study employed data from the Norwegian National Family Record Centre, local parish registers and population censuses. A common ancestor couple (living between 1580 and 1650) was found in six families, and two other families were associated by intermarriage. The remaining two families could not be traced back to either of these ancestors, though chromosome 12q12 haplotype analysis showed p.G2019S carriers shared alleles for 15 markers in the LRRK2 region. The study provides support for a common ancestor in Norwegian families with LRRK2 p.G2019S parkinsonism. The mutation was probably introduced to Norway through tradesmen from Europe. The extended pedigree that now links modern day carriers may help in mapping penetrance modifiers.
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway. krisztina.k.johansen@ntnu.no
authors.forename: Krisztina K
authors.initials: KK
authors.lastname: Johansen
authors.forename: Kåre
authors.initials: K
authors.lastname: Hasselberg
authors.forename: Linda R
authors.initials: LR
authors.lastname: White
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: Jan O
authors.initials: JO
authors.lastname: Aasly
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009664:Norway; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases