title: Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1.
abstract: OBJECTIVE
  To characterize clinical features and identify MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1 (MEN1). Settings Non-profit academic centre.
  
  
  METHODS
  Fourteen Brazilian families with MEN1 and 141 at-risk relatives.
  
  
  RESULTS
  We identified 12 different MEN1 disease-causing mutations, seven of them previously unreported: 308delC; 375del21; 549A>T (I147F); 1243delA; 1348T>G (L413R); 1351T>C (L414P) and 1523G>T (W471C). Families with the recurrent mutations 360delTCTA and L413R were shown to be unrelated by mitochondrial-DNA and Y-chromosome haplotype analyses. Most of the MEN1 single point mutations involved evolutionarily conserved residues, whereas most of the deletion/frameshift changes occurred in GC-rich repetitive regions. Genetic screening of 141 at-risk family members identified 38 MEN1 mutation carriers, 37 (97.4%) of whom had at least one major MEN1-related tumour upon clinical investigation.
  
  
  CONCLUSIONS
  High frequencies of MEN1 gene mutations were detected in Brazilian families with MEN1, including seven new genetic mutations that are predicted to cause inactivation of the MEN1 tumour suppressor gene. Our data underscore the need to implement a systematic MEN1 screening programme in Brazil.
authors.affiliation: Unidade de Endocrinologia Genética LIM-25, Endocrinologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Toledo
authors.forename: Delmar M
authors.initials: DM
authors.lastname: Lourenço
authors.forename: Flavia L
authors.initials: FL
authors.lastname: Coutinho
authors.forename: Elisangela
authors.initials: E
authors.lastname: Quedas
authors.forename: Ivone
authors.initials: I
authors.lastname: Mackowiack
authors.forename: Marcel C C
authors.initials: MC
authors.lastname: Machado
authors.forename: Fabio
authors.initials: F
authors.lastname: Montenegro
authors.forename: Malebranche B C
authors.initials: MB
authors.lastname: Cunha-Neto
authors.forename: Bernardo
authors.initials: B
authors.lastname: Liberman
authors.forename: Maria A A
authors.initials: MA
authors.lastname: Pereira
authors.forename: Pedro H S
authors.initials: PH
authors.lastname: Correa
authors.forename: Sergio P A
authors.initials: SP
authors.lastname: Toledo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D001938:Brazil / Q000453:epidemiology; D005190:Family; D005192:Family Health; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000453:epidemiology* / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins