The goal of this proposal is to identify and clone the gene HRPT2 which is mutated in an autosomal dominant condition, familial hyperparathyroidism-jaw tumor syndrome (HPT-JT) which results in early-onset parathyroid adenomas, fibro-osseous jaw tumors, uterine adenofibromas and occasionally other tumors such as Wilms' tumor. The gene has been mapped by linkage to a 14.5cM region of chromosome 1q25-31, and the region has been narrowed to 0.25 cM by identifying a region of shared haplotype among affected family members in two kindreds. The first specific aim is to identify the gene through sequencing BAC clones covering the region, identifying genes in the region, and screening for mutations in family members. It is expected that 10 to 12 genes will occur in this region of about 250kb, and these will be prioritized for mutation screening by expression in parathyroid glands using an existing parathyroid adenoma library or RT-PCR from parathyroid mRNA.
Specific aim 2 is to characterize the HRPT2 gene by isolating full-length cDNAs and determining the exon-intron structure. Mutations will then be characterized in additional families.
