A Germline Mutation, 1001delC, of the Multiple Endocrine Neoplasia Type 1 (MEN 1) Gene in a Japanese Family.

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder characterized by tumors of the enteropancreas, parathyroid and anterior pituitary. The MEN1 gene was recently cloned, and germline mutations of the gene have been demonstrated in cases of MEN 1. Here, we report a Japanese family with a germline mutation of the MEN1 gene. The proband (44 y.o., male) had primary hyperparathyroidism (PHP) and pancreatic carcinoid, and his older sister (50 y.o.) had a history of parathyroidectomy for primary hyperparathyrodism at the age of 40. Clinical examination revealed no evidence of PHPor other MEN1-related tumors in his son. Direct sequencing analysis revealed a heterozygous germline mutation (lOOldelC) at codon 297 in exon 6 of the MEN1 gene in the proband and his son. Loss of heterozygosity (LOH) was also found in the resected parathyroid tissue of the proband. The deletion of cytosine 1001 observed in this case induces a frame shift, which causes the appearance of a stop codon (TAG) at codon 367. This mutation appears to be associated with tumors of the endocrine tissues in the cases studied. (Internal Medicine 40: 499-505, 2001)

Multiple Endocrine Neoplasia iype 1: Usefulness of Genetic Tests in Atypical Cases

“…Onthe other hand, carcinoid tumors are uncommon in MEN1, but they occasionally occur in lung, thymus and stomach in MEN1 patients (21,22). The atypical MEN1 case described by Wada et al (17) suggests that carcinoid tumors should be considered to occur in the pancreas.…”

“…Nevertheless, identification of the MEN1gene has allowed a definitive diagnosis of MEN1 in the majority of patients with both typical and atypical MEN1 phenotypes (13,15), although some families presenting MEN1 syndromes had no detectable MEN1gene mutation (16). Wadaand colleagues present an interesting case of MEN1 with PHP and pancreatic carcinoid tumors (17). Their patient had neither pituitary tumors nor pancreatic islet tumors, although GRH-producingtumors could not be ruled out.…”