Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS)
Oculo-auriculo-vertebral-spectrum (OAVS; OMIM 164210) is a rare disorder originating from abnormal development of the first and second branchial arch. The clinical phenotype is extremely heterogeneous with ear anomalies, hemifacial microsomia, ocular defects, and vertebral malformations being the ma...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| author | Valentina Guida Luciano Calzari Maria Teresa Fadda Francesca Piceci-Sparascio Maria Cristina Digilio Laura Bernardini Francesco Brancati Teresa Mattina Daniela Melis Francesca Forzano Silvana Briuglia Tommaso Mazza Sebastiano Bianca Enza Maria Valente Leila Bagherjad Salehi Paolo Prontera Mario Pagnoni Romano Tenconi Bruno Dallapiccola Giorgio Iannetti Luigi Corsaro Alessandro De Luca Davide Gentilini |
| author_facet | Valentina Guida Luciano Calzari Maria Teresa Fadda Francesca Piceci-Sparascio Maria Cristina Digilio Laura Bernardini Francesco Brancati Teresa Mattina Daniela Melis Francesca Forzano Silvana Briuglia Tommaso Mazza Sebastiano Bianca Enza Maria Valente Leila Bagherjad Salehi Paolo Prontera Mario Pagnoni Romano Tenconi Bruno Dallapiccola Giorgio Iannetti Luigi Corsaro Alessandro De Luca Davide Gentilini |
| author_sort | Valentina Guida |
| collection | DOAJ |
| description | Oculo-auriculo-vertebral-spectrum (OAVS; OMIM 164210) is a rare disorder originating from abnormal development of the first and second branchial arch. The clinical phenotype is extremely heterogeneous with ear anomalies, hemifacial microsomia, ocular defects, and vertebral malformations being the main features. <i>MYT1</i>, <i>AMIGO2</i>, and <i>ZYG11B</i> gene variants were reported in a few OAVS patients, but the etiology remains largely unknown. A multifactorial origin has been proposed, including the involvement of environmental and epigenetic mechanisms. To identify the epigenetic mechanisms contributing to OAVS, we evaluated the DNA-methylation profiles of 41 OAVS unrelated affected individuals by using a genome-wide microarray-based methylation approach. The analysis was first carried out comparing OAVS patients with controls at the group level. It revealed a moderate epigenetic variation in a large number of genes implicated in basic chromatin dynamics such as DNA packaging and protein-DNA organization. The alternative analysis in individual profiles based on the searching for Stochastic Epigenetic Variants (SEV) identified an increased number of SEVs in OAVS patients compared to controls. Although no recurrent deregulated enriched regions were found, isolated patients harboring suggestive epigenetic deregulations were identified. The recognition of a different DNA methylation pattern in the OAVS cohort and the identification of isolated patients with suggestive epigenetic variations provide consistent evidence for the contribution of epigenetic mechanisms to the etiology of this complex and heterogeneous disorder. |
| first_indexed | 2024-03-09T03:38:34Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:38:34Z |
| publishDate | 2021-01-01 |
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| spelling | doaj.art-85266ac91354400bba77ed6746278dbb2023-12-03T14:44:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223119010.3390/ijms22031190Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS)Valentina Guida0Luciano Calzari1Maria Teresa Fadda2Francesca Piceci-Sparascio3Maria Cristina Digilio4Laura Bernardini5Francesco Brancati6Teresa Mattina7Daniela Melis8Francesca Forzano9Silvana Briuglia10Tommaso Mazza11Sebastiano Bianca12Enza Maria Valente13Leila Bagherjad Salehi14Paolo Prontera15Mario Pagnoni16Romano Tenconi17Bruno Dallapiccola18Giorgio Iannetti19Luigi Corsaro20Alessandro De Luca21Davide Gentilini22Medical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, ItalyIstituto Auxologico Italiano IRCCS, Bioinformatics and Statistical Genomics Unit, Cusano Milanino, 20095 Milano, ItalyDepartment of Maxillofacial Surgery, Sapienza University of Rome, 00161 Rome, ItalyMedical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, ItalyGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00165 Rome, ItalyMedical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, ItalyDepartment of Life, Health and Environmental Sciences, Unit of Medical Genetics University of L’Aquila, 67100 L’Aquila, ItalyMedical Genetics, Department of Biomedical and Biotechnological Sciences, University of Catania, 95131 Catania, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, 84084 Salerno, ItalyClinical Genetics Department, Guy’s & St Thomas’ NHS Foundation Trust, London SE1 7EH, UKMedical Genetics, University of Messina, 98125 Messina, ItalyUnit of Bioinformatics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, ItalyCentro di Consulenza Genetica e Teratologia della Riproduzione, Dipartimento Materno Infantile, ARNAS Garibaldi Nesima, 95123 Catania, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyTor Vergata University Hospital, Medical Genetics Unit, PTV, 00133 Rome, ItalyMedical Genetics Unit, University of Perugia Hospital SM della Misericordia, 06129 Perugia, ItalyDepartment of Maxillofacial Surgery, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Pediatrics, Clinical Genetics, Università di Padova, 35122 Padova, ItalyGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00165 Rome, ItalyDepartment of Maxillofacial Surgery, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, ItalyMedical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, ItalyIstituto Auxologico Italiano IRCCS, Bioinformatics and Statistical Genomics Unit, Cusano Milanino, 20095 Milano, ItalyOculo-auriculo-vertebral-spectrum (OAVS; OMIM 164210) is a rare disorder originating from abnormal development of the first and second branchial arch. The clinical phenotype is extremely heterogeneous with ear anomalies, hemifacial microsomia, ocular defects, and vertebral malformations being the main features. <i>MYT1</i>, <i>AMIGO2</i>, and <i>ZYG11B</i> gene variants were reported in a few OAVS patients, but the etiology remains largely unknown. A multifactorial origin has been proposed, including the involvement of environmental and epigenetic mechanisms. To identify the epigenetic mechanisms contributing to OAVS, we evaluated the DNA-methylation profiles of 41 OAVS unrelated affected individuals by using a genome-wide microarray-based methylation approach. The analysis was first carried out comparing OAVS patients with controls at the group level. It revealed a moderate epigenetic variation in a large number of genes implicated in basic chromatin dynamics such as DNA packaging and protein-DNA organization. The alternative analysis in individual profiles based on the searching for Stochastic Epigenetic Variants (SEV) identified an increased number of SEVs in OAVS patients compared to controls. Although no recurrent deregulated enriched regions were found, isolated patients harboring suggestive epigenetic deregulations were identified. The recognition of a different DNA methylation pattern in the OAVS cohort and the identification of isolated patients with suggestive epigenetic variations provide consistent evidence for the contribution of epigenetic mechanisms to the etiology of this complex and heterogeneous disorder.https://www.mdpi.com/1422-0067/22/3/1190oculo-auriculo-vertebral spectrumOAVSDNA-methylationgenome-wideinfinium human methylation 450K beadchipretinoic acid |
| spellingShingle | Valentina Guida Luciano Calzari Maria Teresa Fadda Francesca Piceci-Sparascio Maria Cristina Digilio Laura Bernardini Francesco Brancati Teresa Mattina Daniela Melis Francesca Forzano Silvana Briuglia Tommaso Mazza Sebastiano Bianca Enza Maria Valente Leila Bagherjad Salehi Paolo Prontera Mario Pagnoni Romano Tenconi Bruno Dallapiccola Giorgio Iannetti Luigi Corsaro Alessandro De Luca Davide Gentilini Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS) International Journal of Molecular Sciences oculo-auriculo-vertebral spectrum OAVS DNA-methylation genome-wide infinium human methylation 450K beadchip retinoic acid |
| title | Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS) |
| title_full | Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS) |
| title_fullStr | Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS) |
| title_full_unstemmed | Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS) |
| title_short | Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS) |
| title_sort | genome wide dna methylation analysis of a cohort of 41 patients affected by oculo auriculo vertebral spectrum oavs |
| topic | oculo-auriculo-vertebral spectrum OAVS DNA-methylation genome-wide infinium human methylation 450K beadchip retinoic acid |
| url | https://www.mdpi.com/1422-0067/22/3/1190 |
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