Faculty Collaboration Database

Genotype-phenotype analysis in multiple endocrine neoplasia type 1. Arch Surg 2002 Jun;137(6):641-7

Date

06/07/2002

Pubmed ID

12049533

DOI

10.1001/archsurg.137.6.641

Scopus ID

2-s2.0-0036269867 (requires institutional sign-in at Scopus site)   121 Citations

Abstract

HYPOTHESIS: Multiple endocrine neoplasia type 1 (MEN 1) syndrome is an autosomal dominant disorder caused by germline mutations in the MEN1 gene and characterized by multiple endocrine tumors, most notably in the parathyroid glands, pituitary, and pancreas. The syndrome demonstrates variable expressivity and considerable genetic heterogeneity. Patient data were examined for possible associations between genotype and phenotype.

DESIGN: We reviewed recorded medical data from 1975 to 2001 on patients with MEN 1 and compared specific types and locations of MEN1 gene mutations with manifestations of the syndrome.

PATIENTS AND RESULTS: We identified 109 affected patients from 24 MEN 1 kindreds. The phenotypic expression of MEN 1 in affected individuals included hyperparathyroidism in 74%, pancreatic endocrine tumors in 51%, and pituitary tumors in 35%. Twelve of 14 insulinomas occurred in patients with pituitary tumors. Mutation analysis was completed in 14 of 24 kindreds (80 of the 109 patients). Mutations were most common in exons 2 (31%), 9 (15%), and 10 (23%). All 21 patients with frameshift mutations (and known pancreatic endocrine tumor status) had such tumors. Pituitary tumors were associated with frameshift mutations in exon 2.

CONCLUSIONS: The type and location of MEN1 mutations may be associated with the phenotypic expression of specific tumors. Such information may assist in the genetic counseling and surveillance of at-risk patients. A specific genotype-phenotype correlation is unlikely because of the heterogeneity of the mutations in the MEN1 gene.

Author List

Kouvaraki MA, Lee JE, Shapiro SE, Gagel RF, Sherman SI, Sellin RV, Cote GJ, Evans DB

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Female
Frameshift Mutation
Genotype
Germ-Line Mutation
Humans
Insulinoma
Male
Middle Aged
Multiple Endocrine Neoplasia Type 1
Neoplasm Proteins
Pancreatic Neoplasms
Phenotype
Pituitary Neoplasms
Proto-Oncogene Proteins
Retrospective Studies