title: Frequency of heterozygous Parkin mutations in healthy subjects: need for careful prospective follow-up examination of mutation carriers.
abstract: The role of single heterozygous mutations in the putatively recessive Parkin gene in Parkinson disease (PD) is a vividly debated issue, partly caused by the largely unknown frequency of these mutations in healthy individuals. We investigated mutations in all 12 Parkin exons in 356 controls from two European populations including individuals from South Tyrol and Germany. None of the controls carried a homozygous or compound heterozygous mutation. Seventeen carriers of rare heterozygous alterations were detected, of which 13 (13/356; 3.7%) are considered to alter protein structure including four different gene dosage alterations, four missense mutations, and two frameshift mutations. Two of the mutations occurred recurrently in the South Tyrolean population. There was no obvious difference in the mutation frequency between the two populations. One of the presumably healthy mutation carrier was available for re-examination at the age of 67 years. He presented with mild signs of parkinsonism but not fulfilling diagnostic criteria for definite PD. To elucidate the role of heterozygosity is important for genetic testing and counseling of mutation carriers. A detailed clinical prospective and follow-up examination of mutation carriers is required for a better understanding of the role of heterozygous Parkin mutations.
authors.affiliation: Schilling Department of Clinical and Molecular Neurogenetics and Department of Neurology, University of Lübeck, Ratzeburger Allee 160, Schleswig-Holstein, 23538 Lübeck, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.forename: Manfred
authors.initials: M
authors.lastname: Mitterer
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Lanthaler
authors.forename: Ana
authors.initials: A
authors.lastname: Djarmati
authors.forename: Johann
authors.initials: J
authors.lastname: Hagenah
authors.forename: Karin
authors.initials: K
authors.lastname: Wiegers
authors.forename: Susen
authors.initials: S
authors.lastname: Winkler
authors.forename: Heike
authors.initials: H
authors.lastname: Pawlack
authors.forename: Thora
authors.initials: T
authors.lastname: Lohnau
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Katja
authors.initials: K
authors.lastname: Lohmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001933:Brain Stem / Q000000981:diagnostic imaging; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005858:Germany; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein