title: Evidence for the founder effect of RET533 as the common Greek and Brazilian ancestor spreading multiple endocrine neoplasia 2A.
abstract: OBJECTIVE
  About one-quarter of patients with medullary thyroid cancer (MTC) have inherited disease due to mutations in theRETgene. A rare mutation in exon 8 (G533C) ofRET, previously described in a large Brazilian family with MEN2A, also appeared to be clustering in Greece, whereas it was rarely reported in other ethnic groups. The aim of this study was to identify a possible common ancestry between these carriers.
  
  
  METHODS
  TwelveRETG533C mutation carriers, four randomly selected from the Brazilian cohort and eight from apparently unrelated Greek families, were studied for a possible common ancestral origin.RETflanking microsatellite markers at chromosome 10q (D10S197, D10S196, D10S1652 and D10S537) were used.
  
  
  RESULTS
  Genomic DNA analysis using these markers showed that many of these apparently unrelated individuals shared a common haplotype indicating a common ancestral origin.
  
  
  CONCLUSIONS
  Our data suggest that Brazilian and Greek patients with MTC carrying the G533C mutation in exon 8 ofRETgene originate from a common ancestor. Due to historical reasons, we speculate that the more plausible explanation for the origin of this mutation is in Greece.
authors.affiliation: Departments of Medicine.
authors.forename: Lucas L
authors.initials: LL
authors.lastname: Cunha
authors.affiliation: Departments of Medicine.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Lindsey
authors.affiliation: Departments of Medicine.
authors.forename: Maria Inez C
authors.initials: MIC
authors.lastname: França
authors.affiliation: Endocrine UnitDepartment of Medical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Leda
authors.initials: L
authors.lastname: Sarika
authors.affiliation: Endocrine UnitDepartment of Medical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Papathoma
authors.affiliation: Departments of Medicine.
authors.forename: Ilda S
authors.initials: IS
authors.lastname: Kunii
authors.affiliation: Morphology and GeneticsEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Janete M
authors.initials: JM
authors.lastname: Cerutti
authors.affiliation: Departments of Medicine.
authors.forename: Magnus R
authors.initials: MR
authors.lastname: Dias-da-Silva
authors.affiliation: Endocrine UnitDepartment of Medical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Alevizaki
authors.affiliation: Departments of Medicine.
authors.forename: Rui M B
authors.initials: RMB
authors.lastname: Maciel
mesh_terms: D000328:Adult; D001938:Brazil / Q000453:epidemiology; D005260:Female; D018703:Founder Effect; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human