FAMILIAL ISOLATED HYPERPARATHYROIDISM CAUSED BY SINGLE ADENOMA - A DISTINCT ENTITY DIFFERENT FROM MULTIPLE ENDOCRINE NEOPLASIA

Familial hyperparathyroidism (FHPT) is a hereditary disease where hype rparathyroidism (HPT) is transmitted in an autosomal dominant fashion. FHPT consists of a variety of diseases such as multiple endocrine neo plasia type1 (MEN 1) and type2 (MEN 2), familial isolated hyperparathy roidism (FIHPT) with single adenoma and with multiple adenomas (or hyp erplasia), and FHPT with jaw-tumor (FHPT-JT). isolation of the genes r esponsible for MEN 1, and 2, i.e. MEN1 and RET, respectively, makes it possible to examine the relations among disorders constituting FHPT. We studied germ-line mutations in these 2 genes in a family of FHPT wi th single parathyroid adenoma. The disorder in this family was proved to be an entity different from MEN 1 because no germ-line mutations in MEN1 gene were found in the affected members. The loss of heterozygos ity (LOH) at MEN1 gene and PYGM were not found in the abnormal parathy roid in this family, supporting the above conclusion. No mutations in exons 10, and 11 of RET proto-oncogene was found in germ-line DNA of t he affected member of the family, suggesting no relation to MEN 2A. Li nkage study excluded the possibility of FHPT-JT syndrome. PRAD1 was no t overexpressed in the parathyroid tumors in this family. The relation of this disorder to FIHPT with multiple enlarged parathyroid glands r emains to be clarified. A search for the gene(s) predisposing to FIHPT is needed.