title: Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases.
abstract: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in parathyroids, enteropancreatic endocrine tissues, anterior pituitary, and other tissues. The gene for MEN1 has recently been cloned and shown to code for a 610-amino acid protein of enigmatic function which probably acts as a tumor suppressor. Several mutations causing the 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 gene by means of an automatic sequencing protocol. Twelve different mutations were identified including nonsense, frameshift, splicing, and missense mutations. Two of these mutations (D172Y and 357del4) occurred more than once. A missense mutation was also found in a kindred with familial hyperparathyroidism. We observed no significant correlation between the nature or position of mutation and the clinical status. We have also detected 6 intragenic polymorphisms and DNA sequence variants and have analyzed their frequencies in our population.
authors.affiliation: Department of Medical Genetics, University Hospital, Univeristé de Liège, Belgium. jponcin@chu.ulg.ac.be
authors.forename: J
authors.initials: J
authors.lastname: Poncin
authors.forename: R
authors.initials: R
authors.lastname: Abs
authors.forename: B
authors.initials: B
authors.lastname: Velkeniers
authors.forename: M
authors.initials: M
authors.lastname: Bonduelle
authors.forename: M
authors.initials: M
authors.lastname: Abramowicz
authors.forename: J J
authors.initials: JJ
authors.lastname: Legros
authors.forename: A
authors.initials: A
authors.lastname: Verloes
authors.forename: M
authors.initials: M
authors.lastname: Meurisse
authors.forename: L
authors.initials: L
authors.lastname: Van Gaal
authors.forename: C
authors.initials: C
authors.lastname: Verellen
authors.forename: L
authors.initials: L
authors.lastname: Koulischer
authors.forename: A
authors.initials: A
authors.lastname: Beckers
mesh_terms: D001530:Belgium; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins
chemical_list: C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins