Novel germline mutations of the MEN1 gene in Japanese patients with multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorde r characterized by tumors of the parathyroid glands, the pancreatic islet c ells, and the anterior pituitary. Germline mutations of the MEN1 gene in th ree independent Japanese cases with MEN1 were analyzed. Case 1 has revealed a 2-bp (TA) insertion at nucleotide position 341 (341insTA) in exon 2, whi ch shifts the reading frame such that the mutant protein has a completely d ifferent amino acid sequence from codon 78 to the premature stop codon at 1 19. In case 2, a nucleotide substitution, i.e., TAG in place of TGG, which encodes tryptophan at codon 198 was identified (nonsense mutation). These m utations were heterozygously present and have not been reported previously. Case 3 showed no mutations in the protein-coding exons and exon-intron jun ctions of the MEN1 gene by single-strand conformation polymorphism or direc t sequencing of the polymerase chain reaction (PCR) fragments. We confirmed the finding that patients with MEN1 carry heterozygous germline mutations in the MEN1 gene, which is compatible with the idea that the MEN1 gene is a tumor suppressor gene. The reason why mutations in the coding region of th e MEN1 gene could not be detected by PCR-based analysis in some of the MEN1 patients, e.g. case 3, needs to be clarified further.