title: Pseudo-autosomal dominant inheritance of PARK2: two families with parkin gene mutations.
abstract: We report two families (Family S and Family N) with early-onset parkinsonism in two generations. The mode of inheritance appeared to be autosomal dominant, however, haplotye analysis suggested linkage to chromosome 6q25.2-27, the PARK2 locus, and all affected members were homozygotes in their haplotypes. In Family S, the affected father was married to unaffected mother, who carried one disease-linked haplotype at chromosome 6q25.2-27. In Family N, the unaffected mother carried one disease-linked haplotype. Quantitative PCR amplification analysis revealed exon 3 deletion in Family S and exon 5 deletion in Family N. The age of onset was from 18 to 22 years in Family S and 25 to 42 years in Family N. In both of their hometowns, most people lived in the same districts for many generations and consanguineous marriages had been common. Thus, the carrier state of the parkin gene might have been high in those communities, and marriage of a patient and a carrier is expected to result in autosomal dominant like inheritance. We conclude that PARK2 cannot be excluded even if the mode of inheritance appears as autosomal dominant, when the affected patients are young.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo, Tokyo 113-8421, Japan. tomo@med.juntendo.ac.jp
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Hiroto
authors.initials: H
authors.lastname: Matsumine
authors.forename: JiaLin
authors.initials: J
authors.lastname: Zhang
authors.forename: Yoko
authors.initials: Y
authors.lastname: Imamichi
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000368:Aged; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020734:Parkinsonian Disorders / Q000235:genetics*; D010375:Pedigree; D044767:Ubiquitin-Protein Ligases
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases