A FAMILY OF MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A - GENETIC-ANALYSIS AND CLINICAL-FEATURES

Since a heterozygous missense mutation of the RET proto-oncogene in th e germline was found to cause multiple endocrine neoplasia type 2A (ME N 2A) in 1993, some 20 different mutations of this gene have been iden tified in MEN 2A kindreds. We report an MEN 2A family in which serine (AGC) substitutes for cysteine (TGC) at codon 618 in exon 10 of the RE T proto-oncogene. The mutation was identified by sequencing PCR produc ts of exons 10 and 11 in the proband. Since this mutation results in c reation of a new cleavage site for Alu I restriction enzyme, most of t he other members of the family were screened by digestion of the PCR p roduct of exon 10 with this enzyme. Eleven of 20 subjects across four generations examined have the mutation of the RET proto-oncogene, and all of the adult gene carriers except one woman had MTC. Characteristi cs of this family are 1) pheochromocytoma has been found in only the p roband, 2) no obvious hyperparathyroidism has been observed, and 3) th e prognosis is favorable, with nobody dying of MEN 2A itself. Genetic analysis of MEN 2A is definitely useful and essential for screening of a MEN 2A family. It is very important to accumulate cases with MEN 2A and investigate the phenotype and the prognosis in each mutation.