Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorde r characterized by tumors in parathyroids, enteropancreatic endocrine tissu es, anterior pituitary, and other tissues. The gene for MEN1 has recently b een cloned and shown to code for a 610-amino acid protein of enigmatic func tion which probably acts as a tumor suppressor. Several mutations causing t he MEN1 phenotype have been recently identified. In order to determine the spectrum of MEN1 gene mutations in a sample of 25 Belgian patients, we have systematically screened the 10 exons and adjacent sequences of the MEN1 ge ne by means of an automatic sequencing protocol. Twelve different mutations were identified including nonsense, frameshift, splicing, and missense mut ations. Two of these mutations ( D172Y and 357del4) occurred more than once . A missense mutation was also found in a kindred with familial hyperparath yroidism. We observed no significant correlation between the nature or posi tion of mutation and the clinical status. We have also detected 6 intrageni c polymorphisms and DNA sequence variants and have analyzed their frequenci es in our population. Hum Mutat 13:54-60, 1999. (C) 1999 Wiley-Liss, Inc.