Localization of a gene for an autosomal recessive form of juvenile parkinsonism to chromosome 6q25.2-27

• Published in: American journal of human genetics Vol. 60; no. 3; pp. 588 - 596
• Main Authors: MATSUMINE, H, SAITO, M, SANPEI, K, KOIKE, R, MORI, H, KONDO, T, MIZUTANI, Y, SCHÄFFER, A. A, YAMAMURA, Y, NAKAMURA, S, KUZUHARA, S, TSUJI, S, SHIMODA-MATSUBAYASHI, S, MIZUNO, Y, TANAKA, H, ISHIKAWA, A, NAKAGAWA-HATTORI, Y, YOKOCHI, M, KOBAYASHI, T, IGARASHI, S, TAKANO, H
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01.03.1997
• Subjects: Adolescent; Adult; Age of Onset; Biological and medical sciences; Child; Chromosome Mapping; Chromosomes, Human, Pair 6; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Genes, Recessive; Genetic Linkage; Humans; Male; Medical sciences; Microsatellite Repeats; Neurology; Parkinson Disease - genetics; Pedigree; Polymorphism, Genetic; Superoxide Dismutase - genetics; Human; Genetic mapping; Nervous system diseases; Linkage; Family study; Chromosome C6; Juvenile character; Genetic disease; Parkinsonism; Autosomal character; Recessive character; Degenerative disease; Child
• ISSN: 0002-9297; 1537-6605

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.