The familial medullary thyroid carcinoma-associated RET E768D mutation in a multiple endocrine neoplasia type 2A case.

THE CLINICAL MANIFESTATIONS of the dominantly inherited multiple endocrine neoplasia type 2 (MEN 2) syndrome (familial medullary thyroid cancer [FMTC], MEN 2A or MEN 2B phenotypes) are determined by the transforming activity and penetrance of specific missense mutations in the ‘‘rearranged during transfection’’ (RET) protooncogene. In addition to medullary thyroid carcinoma (MTC), which is the common feature of all MEN 2 clinical variants and the only manifestation of FMTC, concurrent pheochromocytoma develops in the more aggressive MEN 2A and MEN 2B phenotypes. Pheochromocytoma has been described, although at variable frequencies, in carriers of most RET gene mutations except in those of base substitutions at codons 533, 630, and 768. Hence, the latter mutations have until now been associated exclusively with the FMTC phenotype. Here we report for the first time a MEN 2A patient carrying the germ line Glu768Asp (E768D)