A Family of Multiple Endocrine Neoplasia Type 2A: Genetic Analysis and Clinical Features.

Abstract

Abstract. 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.

Asymmetric Retro‐ and Transfer‐Aldol Reactions Catalyzed by a Simple Chiral Primary Amine

“…It has been reported that mutations at codon 618 lead to a mild form of disease12–14. In one of these reports it was suggested that prophylactic thyroidectomy could be withheld in patients with this mutation until conventional biochemical and imaging examinations turned positive14.…”

“…Nowadays, almost all deaths associated with MEN2A syndromes depend on the aggressiveness of the MTC. Two reports13, 14 claiming that the 618 mutation is linked with mild MTC contained 11 and seven patients with 618 mutations respectively, but no follow‐up data were presented.…”

“…In the Swedish population this corresponds to an annual incidence of 618 mutations of about 0·03 per million inhabitants. It was first reported that mutations at codon 618 lead to a mild form of disease12–14, and one group suggested that prophylactic thyroidectomy could be withheld in patients with this mutation until conventional biochemical and imaging examinations turned positive14. However, when attempting to stratify the RET mutations associated with MTC into intermediate‐, high‐ and highest‐risk levels Kikumori et al 15 suggested that patients with 618 mutations should be included in the high‐risk group.…”