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Park6‐linked parkinsonism occurs in several european families
Author(s) -
Valente Enza Maria,
Brancati Francesco,
Ferraris Alessandro,
Graham Elizabeth A.,
Davis Mary B.,
Breteler Monique M.B.,
Gasser Thomas,
Bonifati Vincenzo,
Bentivoglio Anna Rita,
De Michele Giuseppe,
Dürr Alexandra,
Cortelli Pietro,
Wassilowsky Dietmar,
Harhangi Biswadjiet S.,
Rawal Nina,
Caputo Viviana,
Filla Alessandro,
Meco Giuseppe,
Oostra Ben A.,
Brice Alexis,
Albanese Alberto,
Dallapiccola Bruno,
Wood Nicholas W.
Publication year - 2002
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10053
Subject(s) - parkinsonism , locus (genetics) , genetics , parkin , haplotype , age of onset , dystonia , genetic linkage , biology , proband , disease , medicine , parkinson's disease , gene , genotype , neuroscience , mutation
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.