HEREDITARY HYPERPARATHYROIDISM JAW TUMOR SYNDROME - THE ENDOCRINE TUMOR GENE HRPT2 MAPS TO CHROMOSOME IQ21-Q31

The syndrome of hereditary hyperparathyroidism and jaw tumors (HPT-JT) is characterized by inheritance, in an autosomal dominant pattern, of recurrent parathyroid adenomas, fibro-osseous tumors of the mandible and/or maxilla, Wilms tumor, and parathyroid carcinoma. This syndrome is clinically and genetically distinct from other endocrine neoplasia syndromes and appears to result from mutation of an endocrine tumor ge ne designated ''HRPT2.'' We studied five HPT-JT families (59 persons, 20 affected); using PCR-based markers, we instituted a genomewide link age search after excluding several candidate genes. Lod scores were ca lculated at various recombination fractions (theta), penetrance 90%. W e mapped HRPT2 to the long arm of chromosome 1 (1q21-q31). The maximal lod score was 6.10 at theta = .0 with marker D1S212, or >10(6) odds i n favor of linkage. In six hereditary Wilms tumor families (96 persons , 29 affected), we found no linkage to Iq markers closely linked with HRPT2 (led scores -15.6 [D1S191] and -17.8 [D1S196], theta = .001). Ni ne parathyroid adenomas and one Wilms tumor from nine members of three HPT-JT families were examined for loss of heterozygosity at linked lo ci. The parathyroid adenomas and Wilms tumor showed no loss of heteroz ygosity for these DNA markers. Our data establish that HRPT2, an endoc rine tumor gene on the long arm of chromosome 1, is responsible for th e HPT-JT syndrome but not for the classical hereditary Wilms tumor syn drome.