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NGS analysis in Marfan syndrome spectrum: Combination of rare and common genetic variants to improve genotype-phenotype correlation analysis

The diagnosis of Marfan spectrum includes a large number of clinical criteria. Although the identification of pathogenic variants contributes to the diagnostic process, its value to the prediction of clinical outcomes is still limited. An important novelty of the present study is represented by the...

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Autores principales: Gentilini, Davide, Oliveri, Antonino, Fazia, Teresa, Pini, Alessandro, Marelli, Susan, Bernardinelli, Luisa, Di Blasio, Anna Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752800/
https://www.ncbi.nlm.nih.gov/pubmed/31536524
http://dx.doi.org/10.1371/journal.pone.0222506
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author Gentilini, Davide
Oliveri, Antonino
Fazia, Teresa
Pini, Alessandro
Marelli, Susan
Bernardinelli, Luisa
Di Blasio, Anna Maria
author_facet Gentilini, Davide
Oliveri, Antonino
Fazia, Teresa
Pini, Alessandro
Marelli, Susan
Bernardinelli, Luisa
Di Blasio, Anna Maria
author_sort Gentilini, Davide
collection PubMed
description The diagnosis of Marfan spectrum includes a large number of clinical criteria. Although the identification of pathogenic variants contributes to the diagnostic process, its value to the prediction of clinical outcomes is still limited. An important novelty of the present study is represented by the statistical approach adopted to investigate genotype-phenotype correlation. The analysis has been improved considering the extended genetic information obtained by Next Generation Sequencing (NGS) and combining the effects of both rare and common genetic variants in an inclusive model. To this aim a cohort of 181 patients were analyzed with a NGS panel including 11 genes associated with Marfan spectrum. The genotype-phenotype correlation was also investigated considering the possibility to predict presence of a pathological mutation in Marfan syndrome (MFS) main genes based only on the analysis of phenotypic traits. Results obtained indicate that information about clinical traits can be summarized in a new variable that resulted significantly associated with the probability to find a pathological mutation in MFS main genes. This is important since the choice of the genetic test is often influenced by the phenotypic characterization of patients. Moreover, both rare and common variants were found to significantly contribute to clinical spectrum and their combination allowed to increase the percentage of phenotype variability that could be explained based on genetic factors. Results highlight the opportunity to take advantage of the overall genetic information obtained by NGS data to have a better clinical classification of patients.
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spelling pubmed-67528002019-09-27 NGS analysis in Marfan syndrome spectrum: Combination of rare and common genetic variants to improve genotype-phenotype correlation analysis Gentilini, Davide Oliveri, Antonino Fazia, Teresa Pini, Alessandro Marelli, Susan Bernardinelli, Luisa Di Blasio, Anna Maria PLoS One Research Article The diagnosis of Marfan spectrum includes a large number of clinical criteria. Although the identification of pathogenic variants contributes to the diagnostic process, its value to the prediction of clinical outcomes is still limited. An important novelty of the present study is represented by the statistical approach adopted to investigate genotype-phenotype correlation. The analysis has been improved considering the extended genetic information obtained by Next Generation Sequencing (NGS) and combining the effects of both rare and common genetic variants in an inclusive model. To this aim a cohort of 181 patients were analyzed with a NGS panel including 11 genes associated with Marfan spectrum. The genotype-phenotype correlation was also investigated considering the possibility to predict presence of a pathological mutation in Marfan syndrome (MFS) main genes based only on the analysis of phenotypic traits. Results obtained indicate that information about clinical traits can be summarized in a new variable that resulted significantly associated with the probability to find a pathological mutation in MFS main genes. This is important since the choice of the genetic test is often influenced by the phenotypic characterization of patients. Moreover, both rare and common variants were found to significantly contribute to clinical spectrum and their combination allowed to increase the percentage of phenotype variability that could be explained based on genetic factors. Results highlight the opportunity to take advantage of the overall genetic information obtained by NGS data to have a better clinical classification of patients. Public Library of Science 2019-09-19 /pmc/articles/PMC6752800/ /pubmed/31536524 http://dx.doi.org/10.1371/journal.pone.0222506 Text en © 2019 Gentilini et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Gentilini, Davide
Oliveri, Antonino
Fazia, Teresa
Pini, Alessandro
Marelli, Susan
Bernardinelli, Luisa
Di Blasio, Anna Maria
NGS analysis in Marfan syndrome spectrum: Combination of rare and common genetic variants to improve genotype-phenotype correlation analysis
title NGS analysis in Marfan syndrome spectrum: Combination of rare and common genetic variants to improve genotype-phenotype correlation analysis
title_full NGS analysis in Marfan syndrome spectrum: Combination of rare and common genetic variants to improve genotype-phenotype correlation analysis
title_fullStr NGS analysis in Marfan syndrome spectrum: Combination of rare and common genetic variants to improve genotype-phenotype correlation analysis
title_full_unstemmed NGS analysis in Marfan syndrome spectrum: Combination of rare and common genetic variants to improve genotype-phenotype correlation analysis
title_short NGS analysis in Marfan syndrome spectrum: Combination of rare and common genetic variants to improve genotype-phenotype correlation analysis
title_sort ngs analysis in marfan syndrome spectrum: combination of rare and common genetic variants to improve genotype-phenotype correlation analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752800/
https://www.ncbi.nlm.nih.gov/pubmed/31536524
http://dx.doi.org/10.1371/journal.pone.0222506
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