Keep an Eye on Next Generation Sequencing (NGS) Technology: Secondary Findings and Differential Diagnosis in Inherited Retinal Dystrophies (IRDs)
<b>Background</b>: Next Generation Sequencing (NGS) Technology has represented a revolution in the molecular characterization of Inherited Retinal Dystrophies (IRDs), which are among the most genetically and phenotypically heterogeneous conditions. NGS has allowed the characterization of...
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2025-05-01
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| author | Fabiana D’Esposito Matteo Capobianco Caterina Gagliano Alessandro Avitabile Giuseppe Gagliano Gabriella Esposito Edoardo Dammino Antonio Carotenuto Marco Zeppieri |
| author_facet | Fabiana D’Esposito Matteo Capobianco Caterina Gagliano Alessandro Avitabile Giuseppe Gagliano Gabriella Esposito Edoardo Dammino Antonio Carotenuto Marco Zeppieri |
| author_sort | Fabiana D’Esposito |
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| description | <b>Background</b>: Next Generation Sequencing (NGS) Technology has represented a revolution in the molecular characterization of Inherited Retinal Dystrophies (IRDs), which are among the most genetically and phenotypically heterogeneous conditions. NGS has allowed the characterization of a consistent number of patients affected by IRDs, but at the same time, unexpected results can pose diagnostic dilemmas. <b>Aim</b>: The purpose of this review is to describe possible scenarios as a reference for ophthalmologists and geneticists who are involved in this particularly complex field. <b>Methods</b>: A review of the existing literature has been performed. In addition, examples have been brought, from a series of patients that have been analyzed at the University of Naples “Federico II”-CEINGE Biotecnologie Avanzate “Franco Salvatore”. <b>Results</b>: Unexpected results in the genetic characterization of IRDs are not uncommon. The main findings are additional variants that potentially modify phenotypes, deletions masked by apparent homozygosity, and pathogenic variants leading to phenotypes revisitation. <b>Conclusions</b>: The high genetic and phenotypic heterogeneity characterizing IRDs have been greatly advantaged by the advent of NGS Technology. At the same time, the not uncommon finding of unexpected data poses diagnostic criticisms that need to be addressed. In this review, we describe possible scenarios, and we go through some more complex genotype–phenotype correlations. |
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| spelling | doaj-art-e3fe1cf7974b458987436b1db4d25e9f2025-08-20T02:33:30ZengMDPI AGBiomedicines2227-90592025-05-01135111710.3390/biomedicines13051117Keep an Eye on Next Generation Sequencing (NGS) Technology: Secondary Findings and Differential Diagnosis in Inherited Retinal Dystrophies (IRDs)Fabiana D’Esposito0Matteo Capobianco1Caterina Gagliano2Alessandro Avitabile3Giuseppe Gagliano4Gabriella Esposito5Edoardo Dammino6Antonio Carotenuto7Marco Zeppieri8Imperial College Ophthalmic Research Group (ICORG) Unit, Imperial College, London NW15QH, UKDepartment of Ophthalmology, Catania University San Marco Hospital, 95121 Catania, ItalyDepartment of Medicine and Surgery, University of Enna “Kore”, Piazza dell’Università, 94100 Enna, ItalyDepartment of Ophthalmology, Catania University San Marco Hospital, 95121 Catania, ItalyDepartment of Ophthalmology, Catania University San Marco Hospital, 95121 Catania, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80100 Naples, ItalyDepartment of Ophthalmology, Catania University San Marco Hospital, 95121 Catania, ItalyDepartment of Neurosciences, Reproductive Sciences and Dentistry, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy<b>Background</b>: Next Generation Sequencing (NGS) Technology has represented a revolution in the molecular characterization of Inherited Retinal Dystrophies (IRDs), which are among the most genetically and phenotypically heterogeneous conditions. NGS has allowed the characterization of a consistent number of patients affected by IRDs, but at the same time, unexpected results can pose diagnostic dilemmas. <b>Aim</b>: The purpose of this review is to describe possible scenarios as a reference for ophthalmologists and geneticists who are involved in this particularly complex field. <b>Methods</b>: A review of the existing literature has been performed. In addition, examples have been brought, from a series of patients that have been analyzed at the University of Naples “Federico II”-CEINGE Biotecnologie Avanzate “Franco Salvatore”. <b>Results</b>: Unexpected results in the genetic characterization of IRDs are not uncommon. The main findings are additional variants that potentially modify phenotypes, deletions masked by apparent homozygosity, and pathogenic variants leading to phenotypes revisitation. <b>Conclusions</b>: The high genetic and phenotypic heterogeneity characterizing IRDs have been greatly advantaged by the advent of NGS Technology. At the same time, the not uncommon finding of unexpected data poses diagnostic criticisms that need to be addressed. In this review, we describe possible scenarios, and we go through some more complex genotype–phenotype correlations.https://www.mdpi.com/2227-9059/13/5/1117next generation sequencing NGSNGS incidental findingsNGS secondary findingsinherited retinal dystrophiesgenotype–phenotype correlationmolecular diagnosis |
| spellingShingle | Fabiana D’Esposito Matteo Capobianco Caterina Gagliano Alessandro Avitabile Giuseppe Gagliano Gabriella Esposito Edoardo Dammino Antonio Carotenuto Marco Zeppieri Keep an Eye on Next Generation Sequencing (NGS) Technology: Secondary Findings and Differential Diagnosis in Inherited Retinal Dystrophies (IRDs) Biomedicines next generation sequencing NGS NGS incidental findings NGS secondary findings inherited retinal dystrophies genotype–phenotype correlation molecular diagnosis |
| title | Keep an Eye on Next Generation Sequencing (NGS) Technology: Secondary Findings and Differential Diagnosis in Inherited Retinal Dystrophies (IRDs) |
| title_full | Keep an Eye on Next Generation Sequencing (NGS) Technology: Secondary Findings and Differential Diagnosis in Inherited Retinal Dystrophies (IRDs) |
| title_fullStr | Keep an Eye on Next Generation Sequencing (NGS) Technology: Secondary Findings and Differential Diagnosis in Inherited Retinal Dystrophies (IRDs) |
| title_full_unstemmed | Keep an Eye on Next Generation Sequencing (NGS) Technology: Secondary Findings and Differential Diagnosis in Inherited Retinal Dystrophies (IRDs) |
| title_short | Keep an Eye on Next Generation Sequencing (NGS) Technology: Secondary Findings and Differential Diagnosis in Inherited Retinal Dystrophies (IRDs) |
| title_sort | keep an eye on next generation sequencing ngs technology secondary findings and differential diagnosis in inherited retinal dystrophies irds |
| topic | next generation sequencing NGS NGS incidental findings NGS secondary findings inherited retinal dystrophies genotype–phenotype correlation molecular diagnosis |
| url | https://www.mdpi.com/2227-9059/13/5/1117 |
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