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Methylome Profiling in Fabry Disease in Clinical Practice: A Proof of Concept

Anderson–Fabry disease (FD) is an X-linked disease caused by a functional deficit of the α-galactosidase A enzyme. FD diagnosis relies on the clinical manifestations and research of GLA gene mutations. However, because of the lack of a clear genotype/phenotype correlation, FD diagnosis can be challe...

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Autores principales: Di Risi, Teodolinda, Cuomo, Mariella, Vinciguerra, Roberta, Ferraro, Sara, Della Monica, Rosa, Costabile, Davide, Buonaiuto, Michela, Trio, Federica, Capoluongo, Ettore, Visconti, Roberta, Riccio, Eleonora, Pisani, Antonio, Chiariotti, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602470/
https://www.ncbi.nlm.nih.gov/pubmed/36292965
http://dx.doi.org/10.3390/ijms232012110
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author Di Risi, Teodolinda
Cuomo, Mariella
Vinciguerra, Roberta
Ferraro, Sara
Della Monica, Rosa
Costabile, Davide
Buonaiuto, Michela
Trio, Federica
Capoluongo, Ettore
Visconti, Roberta
Riccio, Eleonora
Pisani, Antonio
Chiariotti, Lorenzo
author_facet Di Risi, Teodolinda
Cuomo, Mariella
Vinciguerra, Roberta
Ferraro, Sara
Della Monica, Rosa
Costabile, Davide
Buonaiuto, Michela
Trio, Federica
Capoluongo, Ettore
Visconti, Roberta
Riccio, Eleonora
Pisani, Antonio
Chiariotti, Lorenzo
author_sort Di Risi, Teodolinda
collection PubMed
description Anderson–Fabry disease (FD) is an X-linked disease caused by a functional deficit of the α-galactosidase A enzyme. FD diagnosis relies on the clinical manifestations and research of GLA gene mutations. However, because of the lack of a clear genotype/phenotype correlation, FD diagnosis can be challenging. Recently, several studies have highlighted the importance of investigating DNA methylation patterns for confirming the correct diagnosis of different rare Mendelian diseases, but to date, no such studies have been reported for FD. Thus, in the present investigation, we analyzed for the first time the genome-wide methylation profile of a well-characterized cohort of patients with Fabry disease. We profiled the methylation status of about 850,000 CpG sites in 5 FD patients, all carrying the same mutation in the GLA gene (exon 6 c.901C>G) and presenting comparable low levels of α-Gal A activity. We found that, although the whole methylome profile did not discriminate the FD group from the unaffected one, several genes were significantly differentially methylated in Fabry patients. Thus, we provide here a proof of concept, to be tested in patients with different mutations and in a larger cohort, that the methylation state of specific genes can potentially identify Fabry patients and possibly predict organ involvement and disease evolution.
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spelling pubmed-96024702022-10-27 Methylome Profiling in Fabry Disease in Clinical Practice: A Proof of Concept Di Risi, Teodolinda Cuomo, Mariella Vinciguerra, Roberta Ferraro, Sara Della Monica, Rosa Costabile, Davide Buonaiuto, Michela Trio, Federica Capoluongo, Ettore Visconti, Roberta Riccio, Eleonora Pisani, Antonio Chiariotti, Lorenzo Int J Mol Sci Article Anderson–Fabry disease (FD) is an X-linked disease caused by a functional deficit of the α-galactosidase A enzyme. FD diagnosis relies on the clinical manifestations and research of GLA gene mutations. However, because of the lack of a clear genotype/phenotype correlation, FD diagnosis can be challenging. Recently, several studies have highlighted the importance of investigating DNA methylation patterns for confirming the correct diagnosis of different rare Mendelian diseases, but to date, no such studies have been reported for FD. Thus, in the present investigation, we analyzed for the first time the genome-wide methylation profile of a well-characterized cohort of patients with Fabry disease. We profiled the methylation status of about 850,000 CpG sites in 5 FD patients, all carrying the same mutation in the GLA gene (exon 6 c.901C>G) and presenting comparable low levels of α-Gal A activity. We found that, although the whole methylome profile did not discriminate the FD group from the unaffected one, several genes were significantly differentially methylated in Fabry patients. Thus, we provide here a proof of concept, to be tested in patients with different mutations and in a larger cohort, that the methylation state of specific genes can potentially identify Fabry patients and possibly predict organ involvement and disease evolution. MDPI 2022-10-11 /pmc/articles/PMC9602470/ /pubmed/36292965 http://dx.doi.org/10.3390/ijms232012110 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Di Risi, Teodolinda
Cuomo, Mariella
Vinciguerra, Roberta
Ferraro, Sara
Della Monica, Rosa
Costabile, Davide
Buonaiuto, Michela
Trio, Federica
Capoluongo, Ettore
Visconti, Roberta
Riccio, Eleonora
Pisani, Antonio
Chiariotti, Lorenzo
Methylome Profiling in Fabry Disease in Clinical Practice: A Proof of Concept
title Methylome Profiling in Fabry Disease in Clinical Practice: A Proof of Concept
title_full Methylome Profiling in Fabry Disease in Clinical Practice: A Proof of Concept
title_fullStr Methylome Profiling in Fabry Disease in Clinical Practice: A Proof of Concept
title_full_unstemmed Methylome Profiling in Fabry Disease in Clinical Practice: A Proof of Concept
title_short Methylome Profiling in Fabry Disease in Clinical Practice: A Proof of Concept
title_sort methylome profiling in fabry disease in clinical practice: a proof of concept
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602470/
https://www.ncbi.nlm.nih.gov/pubmed/36292965
http://dx.doi.org/10.3390/ijms232012110
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