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APC and MUTYH Analysis in FAP Patients: A Novel Mutation in APC Gene and Genotype-Phenotype Correlation

APC and MUTYH genes are mutated in 70–90% and 10–30% of familial adenomatous polyposis cases (FAP) respectively. An association between mutation localization and FAP clinical phenotype is reported. The aims of this study were to determine APC and MUTYH mutational status in a small cohort of FAP pati...

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Autores principales: D’Elia, Giovanna, Caliendo, Gemma, Casamassimi, Amelia, Cioffi, Michele, Molinari, Anna Maria, Vietri, Maria Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071208/
https://www.ncbi.nlm.nih.gov/pubmed/29954149
http://dx.doi.org/10.3390/genes9070322
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author D’Elia, Giovanna
Caliendo, Gemma
Casamassimi, Amelia
Cioffi, Michele
Molinari, Anna Maria
Vietri, Maria Teresa
author_facet D’Elia, Giovanna
Caliendo, Gemma
Casamassimi, Amelia
Cioffi, Michele
Molinari, Anna Maria
Vietri, Maria Teresa
author_sort D’Elia, Giovanna
collection PubMed
description APC and MUTYH genes are mutated in 70–90% and 10–30% of familial adenomatous polyposis cases (FAP) respectively. An association between mutation localization and FAP clinical phenotype is reported. The aims of this study were to determine APC and MUTYH mutational status in a small cohort of FAP patients and to evaluate the genotype-phenotype correlation in mutated patients. Here, we report the identification of a novel APC germline mutation, c.510_511insA. Overall, mutational analysis showed pathogenic mutations in 6/10 patients: 5/10 in APC and 1/10 in MUTYH. Additionally, we found three variants of unknown significance in MUTYH gene that showed no evidence of possible splicing defects by in silico analysis. Molecular analysis was also extended to family members of mutated patients. A genotype-phenotype correlation was observed for colonic signs whereas a variation of disease onset age was revealed for the same mutation. Moreover, we found an intrafamilial variability of FAP onset age. Regarding extracolonic manifestations, the development of desmoid tumors was related to surgery and not to mutation position, while a genotype-phenotype correspondence was observed for the onset of thyroid or gastric cancer. These findings can be useful in association to clinical data for early surveillance and suitable treatment of FAP patients.
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spelling pubmed-60712082018-08-09 APC and MUTYH Analysis in FAP Patients: A Novel Mutation in APC Gene and Genotype-Phenotype Correlation D’Elia, Giovanna Caliendo, Gemma Casamassimi, Amelia Cioffi, Michele Molinari, Anna Maria Vietri, Maria Teresa Genes (Basel) Brief Report APC and MUTYH genes are mutated in 70–90% and 10–30% of familial adenomatous polyposis cases (FAP) respectively. An association between mutation localization and FAP clinical phenotype is reported. The aims of this study were to determine APC and MUTYH mutational status in a small cohort of FAP patients and to evaluate the genotype-phenotype correlation in mutated patients. Here, we report the identification of a novel APC germline mutation, c.510_511insA. Overall, mutational analysis showed pathogenic mutations in 6/10 patients: 5/10 in APC and 1/10 in MUTYH. Additionally, we found three variants of unknown significance in MUTYH gene that showed no evidence of possible splicing defects by in silico analysis. Molecular analysis was also extended to family members of mutated patients. A genotype-phenotype correlation was observed for colonic signs whereas a variation of disease onset age was revealed for the same mutation. Moreover, we found an intrafamilial variability of FAP onset age. Regarding extracolonic manifestations, the development of desmoid tumors was related to surgery and not to mutation position, while a genotype-phenotype correspondence was observed for the onset of thyroid or gastric cancer. These findings can be useful in association to clinical data for early surveillance and suitable treatment of FAP patients. MDPI 2018-06-27 /pmc/articles/PMC6071208/ /pubmed/29954149 http://dx.doi.org/10.3390/genes9070322 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
D’Elia, Giovanna
Caliendo, Gemma
Casamassimi, Amelia
Cioffi, Michele
Molinari, Anna Maria
Vietri, Maria Teresa
APC and MUTYH Analysis in FAP Patients: A Novel Mutation in APC Gene and Genotype-Phenotype Correlation
title APC and MUTYH Analysis in FAP Patients: A Novel Mutation in APC Gene and Genotype-Phenotype Correlation
title_full APC and MUTYH Analysis in FAP Patients: A Novel Mutation in APC Gene and Genotype-Phenotype Correlation
title_fullStr APC and MUTYH Analysis in FAP Patients: A Novel Mutation in APC Gene and Genotype-Phenotype Correlation
title_full_unstemmed APC and MUTYH Analysis in FAP Patients: A Novel Mutation in APC Gene and Genotype-Phenotype Correlation
title_short APC and MUTYH Analysis in FAP Patients: A Novel Mutation in APC Gene and Genotype-Phenotype Correlation
title_sort apc and mutyh analysis in fap patients: a novel mutation in apc gene and genotype-phenotype correlation
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071208/
https://www.ncbi.nlm.nih.gov/pubmed/29954149
http://dx.doi.org/10.3390/genes9070322
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