title: PARK6-linked parkinsonism occurs in several European families.
abstract: The Parkin gene on 6q25.2-27 is responsible for about 50% of autosomal recessive juvenile parkinsonism and less than 20% of sporadic early-onset cases. We recently mapped a novel locus for early-onset parkinsonism (PARK6) on chromosome 1p35-p36 in a large family from Sicily. We now confirm linkage to PARK6 in eight additional families with Parkin-negative autosomal recessive juvenile parkinsonism from four different European countries. The maximum cumulative pairwise LOD score was 5.39 for marker D1S478. Multipoint linkage analysis gave the highest cumulative LOD score of 6.29 for marker D1S478. Haplotype construction and determination of the smallest region of homozygosity in one consanguineous family has reduced the candidate interval to a 9cM region between markers D1S483 and D1S2674. No common haplotype could be detected, excluding a common founder effect. These families share some clinical features with the phenotype reported for European Parkin-positive cases, with a wide range of ages at onset (up to 68 yrs) and slow progression. However, features typical of autosomal recessive juvenile parkinsonism, including dystonia at onset and sleep benefit, were not observed in PARK6-linked families, thus making the clinical presentation of late-onset cases indistinguishable from idiopathic Parkinson's disease. PARK6 appears to be an important locus for early-onset parkinsonism in European Parkin-negative patients.
authors.affiliation: Institute for Medical Genetics C.S.S. Mendel, Rome, Italy.
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferraris
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Graham
authors.forename: Mary B
authors.initials: MB
authors.lastname: Davis
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bonifati
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bentivoglio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Michele
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.forename: Dietmar
authors.initials: D
authors.lastname: Wassilowsky
authors.forename: Biswadjiet S
authors.initials: BS
authors.lastname: Harhangi
authors.forename: Nina
authors.initials: N
authors.lastname: Rawal
authors.forename: Viviana
authors.initials: V
authors.lastname: Caputo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Meco
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Alberto
authors.initials: A
authors.lastname: Albanese
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
mesh_terms: D000328:Adult; D017668:Age of Onset; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002878:Chromosomes, Human, Pair 1; D005060:Europe; D005192:Family Health; D005260:Female; D018703:Founder Effect; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa