<Original>A Novel MEN1 Gene Mutation in Leukocyte and Parathyroid Tumors of a MEN Type 1 Patient

概要

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Multiple endocrine neoplasia type 1 (MEN1) is an inherited genomic disorder involving the MEN1 tumor suppressor gene. Many germline mutations of the gene have been previously reported. We identified a novel MEN1 germline mutation in the DNA of a Japanese patient with MEN1. This 48-year-old woman had multiple parathyroid adenomas, a parathyroid carcinoma, a pituitary adenoma, a gastrin-producing islet cell tumor, and multiple gastric carcinoid tumors. Molecular analysis revealed a heterozygous germline mutation : one base T deletion at codon 447 in exon 9 (1451 delT). This case is an isolated incident and none of her relatives was recognized as inheriting MEN1. In the DNA of the resected parathyroid adenoma, only the 1451 delT mutation was detected and an intact allele was missing. The mutation predicts a shift in the reading frame, making a stop signal at codon 457. The mutant gene then will produce defective menin protein with a truncated C-terminal and no nuclear localization signals. These defects seem to make the menin nonfunctional in the nucleus. No intact MEN1 allele was detected in the parathyroid adenoma and mutation of both MEN1 alleles might cause tumor growth. It is highly likely that this genetic abnormality causes multiple endocrine tumors in the patient.
福井大学の論文
2002-12-20