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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2013

Open Access 01-12-2013 | Research

Mutational spectrum of the APC and MUTYH genes and genotype–phenotype correlations in Brazilian FAP, AFAP, and MAP patients

Authors: Giovana Tardin Torrezan, Felipe Cavalcanti Carneiro da Silva, Érika Maria Monteiro Santos, Ana Cristina Victorino Krepischi, Maria Isabel Waddington Achatz, Samuel Aguiar Junior, Benedito Mauro Rossi, Dirce Maria Carraro

Published in: Orphanet Journal of Rare Diseases | Issue 1/2013

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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.
Appendix
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Metadata
Title
Mutational spectrum of the APC and MUTYH genes and genotype–phenotype correlations in Brazilian FAP, AFAP, and MAP patients
Authors
Giovana Tardin Torrezan
Felipe Cavalcanti Carneiro da Silva
Érika Maria Monteiro Santos
Ana Cristina Victorino Krepischi
Maria Isabel Waddington Achatz
Samuel Aguiar Junior
Benedito Mauro Rossi
Dirce Maria Carraro
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2013
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-8-54

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