Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27.
An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 600116) is a levodopa-responsive Parkinsonism whose pathological finding is a highly selective degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. By linkage analysis of diallelic polymorphism of the Mn-superoxide dismutase gene (SOD2), we found a family with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumulative pairwise LOD scores of 7.26 and 7.71 at D6S305 (theta = .03) and D6S253 (theta = .02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons.
Matsumine
H
H
Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
Saito
M
M
Shimoda-Matsubayashi
S
S
Tanaka
H
H
Ishikawa
A
A
Nakagawa-Hattori
Y
Y
Yokochi
M
M
Kobayashi
T
T
Igarashi
S
S
Takano
H
H
Sanpei
K
K
Koike
R
R
Mori
H
H
Kondo
T
T
Mizutani
Y
Y
Schäffer
A A
AA
Yamamura
Y
Y
Nakamura
S
S
Kuzuhara
S
S
Tsuji
S
S
Mizuno
Y
Y
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000235:genetics
D013482:Superoxide Dismutase