Germline Mutation of Type 1 (MEN1) Gene Hyperparathyroidism

Familial primary hyperparathyroidism (FHP) is a rare hereditary disorder characterized by isolated parathyroid tumors without any other lesions related to multiple endocrine neoplasia (MEN). Primary hyperparathyroidism is usually expressed at an early age and is highly penetrated in MEN type 1(MEN1), suggesting that some FHP may be a variant type or early stage of MEN1. The MEN1 gene has recently been cloned and its germline mutations have been considered to play an important role in the tumorigenesis of MEN1. We studied a Japanese family with primary hyperparathyroidism which included 4 patients. To investigate the possible relationship between primary hyperparathyroidism in this family and the MEN1 gene, we analyzed a proband for a germline mutation of the MEN1 gene in this study. We identified a novel heterozygous mutation (1350de13) at codon 414 in exon 9. Restriction digestion analysis revealed the same mutation pattern in his brother with hyperparathyroidism. These findings suggest that our patients may belong to a variant type of MEN1.

[1]  J. Takahara,et al.  Molecular Cloning and Gene Expression of Growth Hormone-Releasing Peptide Receptor in Rat Tissues , 1998, Peptides.

[2]  F. Collins,et al.  Menin, the product of the MEN1 gene, is a nuclear protein. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Kameya,et al.  Germline Mutations of the MEN1 Gene in Japanese Kindred with Multiple Endocrine Neoplasia Type 1 , 1997, Japanese journal of cancer research : Gann.

[4]  C. Larsson,et al.  Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1. , 1997, Human molecular genetics.

[5]  F. Collins,et al.  Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. , 1997, Human molecular genetics.

[6]  Y Wang,et al.  Positional cloning of the gene for multiple endocrine neoplasia-type 1. , 1997, Science.

[7]  C. Edwards,et al.  Clinical studies of multiple endocrine neoplasia type 1 (MEN1) , 1996, QJM : monthly journal of the Association of Physicians.

[8]  L. Rosenberg,et al.  Reviews, Notes, and Listings: When Others Must Choose: Deciding for Patients without Capacity , 1993, Annals of Internal Medicine.

[9]  J. Norton,et al.  Allelic loss from chromosome 11 in parathyroid tumors. , 1992, Cancer research.

[10]  C. Larsson,et al.  Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma , 1988, Nature.

[11]  A. Knudson.  Hereditary cancer, oncogenes, and antioncogenes. , 1985, Cancer research.

[12]  R. Lasker,et al.  Familial hypocalciuric hypercalcemia. The relation to primary parathyroid hyperplasia , 1982 .

[13]  C. Jackson,et al.  The relationship of hereditary hyperparathyroidism to endocrine adenomatosis. , 1967, The American journal of medicine.

[14]  R. Hartsock,et al.  FAMILIAL MULTIPLE ENDOCRINE ADENOMA‐PEPTIC ULCER COMPLEX , 1964, Medicine.

[15]  R. Cutler,et al.  FAMILIAL HYPERPARATHYROIDISM. A KINDRED INVOLVING ELEVEN CASES, WITH A DISCUSSION OF PRIMARY CHIEF-CELL HYPERPLASIA. , 1964, The New England journal of medicine.

[16]  C. Jackson.  Hereditary hyperparathyroidism associated with recurrent pancreatitis. , 1958, Annals of internal medicine.

[17]  P. Wermer.  Genetic aspects of adenomatosis of endocrine glands. , 1954, The American journal of medicine.