title: Mutational spectrum of the APC and MUTYH genes and genotype-phenotype correlations in Brazilian FAP, AFAP, and MAP patients.
abstract: BACKGROUND
  Patients with multiple colorectal adenomas are currently screened for germline mutations in two genes, APC and MUTYH. APC-mutated patients present classic or attenuated familial adenomatous polyposis (FAP/AFAP), while patients carrying biallelic MUTYH mutations exhibit MUTYH-associated polyposis (MAP). The spectrum of mutations as well as the genotype-phenotype correlations in polyposis syndromes present clinical impact and can be population specific, making important to obtain genetic and clinical data from different populations.
  
  
  METHODS
  DNA sequencing of the complete coding region of the APC and MUTYH genes was performed in 23 unrelated Brazilian polyposis patients. In addition, mutation-negative patients were screened for large genomic rearrangements by multiplex ligation-dependent probe amplification, array-comparative genomic hybridization, and duplex quantitative PCR. Biallelic MUTYH mutations were confirmed by allele-specific PCR. Clinical data of the index cases and their affected relatives were used to assess genotype-phenotype correlations.
  
  
  RESULTS
  Pathogenic mutations were identified in 20 of the 23 probands (87%): 14 in the APC gene and six in the MUTYH gene; six of them (30%) were described for the first time in this series. Genotype-phenotype correlations revealed divergent results compared with those described in other studies, particularly regarding the extent of polyposis and the occurrence of desmoid tumors in families with mutations before codon 1444 (6/8 families with desmoid).
  
  
  CONCLUSIONS
  This first comprehensive investigation of the APC and MUTYH mutation spectrum in Brazilian polyposis patients showed a high detection rate and identified novel pathogenic mutations. Notably, a significant number of APC-positive families were not consistent with the predicted genotype-phenotype correlations from other populations.
authors.affiliation: Laboratory of Genomics and Molecular Biology, A.C. Camargo Hospital, São Paulo, SP, Brazil.
authors.forename: Giovana Tardin
authors.initials: GT
authors.lastname: Torrezan
authors.forename: Felipe Cavalcanti Carneiro
authors.initials: FC
authors.lastname: da Silva
authors.forename: Erika Maria Monteiro
authors.initials: EM
authors.lastname: Santos
authors.forename: Ana Cristina Victorino
authors.initials: AC
authors.lastname: Krepischi
authors.forename: Maria Isabel Waddington
authors.initials: MI
authors.lastname: Achatz
authors.forename: Samuel
authors.initials: S
authors.lastname: Aguiar
authors.forename: Benedito Mauro
authors.initials: BM
authors.lastname: Rossi
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000483:Alleles; D001938:Brazil; D015179:Colorectal Neoplasms / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
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