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

Am J Hum Genet. 1997 Mar;60(3):588-96.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 6*
  • Female
  • Genes, Recessive*
  • Genetic Linkage
  • Humans
  • Male
  • Microsatellite Repeats
  • Parkinson Disease / genetics*
  • Pedigree
  • Polymorphism, Genetic
  • Superoxide Dismutase / genetics

Substances

  • Superoxide Dismutase