Criteria for mutation analysis in MEN 1-suspected patients: MEN 1 case-finding

Eur J Clin Invest. 2000 Jun;30(6):487-92. doi: 10.1046/j.1365-2362.2000.00664.x.

Abstract

Background: Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal, dominantly inherited cancer syndrome, with tumours in various endocrine glands. In 1997 the responsible tumour suppressor gene was identified. MEN1 gene germ-line mutations are detected in the vast majority of MEN 1 patients, however, with regard to case-finding, unfortunately only at a very low frequency in patients with apparently sporadic MEN 1-related tumours. In order to increase the detection rate of disease gene carriers among patients with apparently sporadic MEN 1-related tumours, clinical criteria were needed.

Design and results: In this study MEN1 gene germ-line mutations were revealed in 16/16 MEN 1 patients/families (100%). Based on our clinical experience with MEN 1 patients/families we formulated clinical criteria to identify disease gene carriers among patients with apparently sporadic MEN 1-related tumours. The criteria for MEN 1-suspected patients are: young age at onset (< 35 years) and/or multiple MEN 1-related lesions in a single organ or two distinct organs affected. Application of these criteria yielded MEN1 gene germ-line mutations in nine of 15 MEN 1-suspected patients (60%), thus identifying novel MEN 1 families. Follow up was also guaranteed for patients not fulfilling these criteria.

Conclusions: The clinical criteria for MEN 1-suspected patients increase the detection rate of germ-line MEN1 gene mutations among patients with apparently sporadic MEN 1-related tumours. These criteria may be used for (presymptomatic) identification of MEN 1 disease gene-carriers, thus enabling early detection of tumour development and timely treatment, as well as genetic counselling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • DNA Mutational Analysis / methods*
  • DNA, Neoplasm / isolation & purification
  • Exons
  • Family Health
  • Female
  • Genetic Testing / methods*
  • Germ-Line Mutation*
  • Humans
  • Introns
  • Male
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 1 / diagnosis*
  • Multiple Endocrine Neoplasia Type 1 / genetics*
  • RNA, Neoplasm / isolation & purification

Substances

  • DNA, Neoplasm
  • RNA, Neoplasm