Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36

Abstract

Although the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Parkin gene, and recently a second gene, PARK6, involved in early-onset recessive parkinsonism was localized on chromosome 1p35-36. We identified a family segregating early-onset parkinsonism with multiple consanguinity loops in a genetically isolated population. Homozygosity mapping resulted in significant evidence for linkage on chromosome 1p36. Multipoint linkage analysis using MAPMAKER-HOMOZ generated a maximum LOD-score of 4.3, with nine markers spanning a disease haplotype of 16 cM. On the basis of several recombination events, the region defining the disease haplotype can be clearly separated, by > or =25 cM, from the more centromeric PARK6 locus on chromosome 1p35-36. Therefore, we conclude that we have identified on chromosome 1 a second locus, PARK7, involved in autosomal recessive, early-onset parkinsonism.

Figure 1

Pedigree of family with autosomal recessive early-onset parkinsonism, and haplotypes of marker loci spanning the linked region on chromosome 1p36. To protect patient confidentiality, a diamond symbol has been used to mask the sex of all family members. Individuals VI-2, VI-3, and VII-1–VII-7 were examined clinically. Black symbols indicate definitely affected individuals; black bars denote the disease-associated haplotype.