A Family of Multiple Endocrine Neoplasia Type 2A

Genetic Analysis and Clinical Features

抄録

Since a heterozygous missense mutation of the RET proto-oncogene in the germline was found to cause multiple endocrine neoplasia type 2A (MEN 2A) in 1993, some 20 different mutations of this gene have been identified 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 RET proto-oncogene. The mutation was identified by sequencing PCR products of exons 10 and 11 in the proband. Since this mutation results in creation of a new cleavage site for Alu I restriction enzyme, most of the other members of the family were screened by digestion of the PCR product 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. Characteristics of this family are 1) pheochromocytoma has been found in only the proband, 2) no obvious hyperparathyroidism has been observed, and 3) the 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.