TY - JOUR
T1 - PARK6-linked parkinsonism occurs in several European families
AU - Valente, Enza Maria
AU - Brancati, Francesco
AU - Ferraris, Alessandro
AU - Graham, Elizabeth A.
AU - Davis, Mary B.
AU - Breteler, Monique M B
AU - Gasser, Thomas
AU - Bonifati, Vincenzo
AU - Bentivoglio, Anna Rita
AU - De Michele, Giuseppe
AU - Drr, Alexandra
AU - Cortelli, Pietro
AU - Wassilowsky, Dietmar
AU - Harhangi, Biswadjiet S.
AU - Rawal, Nina
AU - Caputo, Viviana
AU - Filla, Alessandro
AU - Meco, Giuseppe
AU - Oostra, Ben A.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1002/ana.10053
DO - 10.1002/ana.10053
M3 - Article
C2 - 11782979
AN - SCOPUS:0036136951
VL - 51
SP - 14
EP - 18
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 1
ER -