title: MEN1 gene mutations in Hungarian patients with multiple endocrine neoplasia type 1.
abstract: OBJECTIVE
  Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder associated with mutations of the MEN1 gene. MEN1 may present as a familial or a sporadic disorder, with multiple endocrine tumours including parathyroid adenomas or hyperplasias, and pancreatic endocrine and pituitary gland tumours. The aim of this study was to examine the prevalence and spectrum of MEN1 gene mutations in Hungarian patients with familial and sporadic MEN1 and in those with a MEN1-related state.
  
  
  METHODS
  Mutation analysis, using temporal temperature gradient gel electrophoresis and direct sequencing of all coding exons and the corresponding exon-intron boundaries of the MEN1 gene, was performed.
  
  
  METHODS
  Peripheral blood DNA was obtained from 32 patients (19 index patients with familial or sporadic MEN1 and 13 index patients with familial or sporadic MEN1-related state). First degree relatives were also studied.
  
  
  RESULTS
  Ten different MEN1 gene mutations were identified in 10 index patients, including four novel mutations (A91V, G28A and E26X all in exon 2, and L301R in exon 6). All but one mutation occurred in index patients with familial or sporadic MEN1; the prevalence of mutation was considerably higher in index patients with familial MEN1 (6/6 patients, 100%) than in those with sporadic MEN1 (3/13 patients, 23%). Of the 13 index patients with a MEN1-related state, only one patient with recurrent isolated primary hyperparathyroidism had a MEN1 gene mutation. Family screening indicated mutations in six symptomatic and in one asymptomatic first degree relative.
  
  
  CONCLUSIONS
  These results confirm previous reports on the high prevalence of novel MEN1 gene mutations among patients with MEN1, and support the questionable efficacy of mutation screening in patients with sporadic MEN1-related states.
authors.affiliation: 2nd Department of Medicine, Faculty of Medicine, Semmelweis Unievrsity, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Balogh
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hunyady
authors.forename: Attila
authors.initials: A
authors.lastname: Patocs
authors.forename: Peter
authors.initials: P
authors.lastname: Gergics
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Valkusz
authors.forename: Miklos
authors.initials: M
authors.lastname: Toth
authors.forename: Karoly
authors.initials: K
authors.lastname: Racz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D019143:Evolution, Molecular; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D006814:Hungary; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D016415:Sequence Alignment