Use of Next-Generation Sequencing for the Molecular Diagnosis of 1,102 Patients With a Autosomal Optic Neuropathy
Advances in next-generation sequencing (NGS) facilitate the diagnosis of genetic disorders. To evaluate its use for the molecular diagnosis of inherited optic neuropathy (ION), a blinding disease caused by the degeneration of retinal ganglion cells, we performed genetic analysis using targeted NGS o...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.602979/full |
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| author | Majida Charif Majida Charif Céline Bris Céline Bris David Goudenège David Goudenège Valérie Desquiret-Dumas Valérie Desquiret-Dumas Estelle Colin Estelle Colin Alban Ziegler Alban Ziegler Vincent Procaccio Vincent Procaccio Pascal Reynier Pascal Reynier Dominique Bonneau Dominique Bonneau Guy Lenaers Patrizia Amati-Bonneau Patrizia Amati-Bonneau |
| author_facet | Majida Charif Majida Charif Céline Bris Céline Bris David Goudenège David Goudenège Valérie Desquiret-Dumas Valérie Desquiret-Dumas Estelle Colin Estelle Colin Alban Ziegler Alban Ziegler Vincent Procaccio Vincent Procaccio Pascal Reynier Pascal Reynier Dominique Bonneau Dominique Bonneau Guy Lenaers Patrizia Amati-Bonneau Patrizia Amati-Bonneau |
| author_sort | Majida Charif |
| collection | DOAJ |
| description | Advances in next-generation sequencing (NGS) facilitate the diagnosis of genetic disorders. To evaluate its use for the molecular diagnosis of inherited optic neuropathy (ION), a blinding disease caused by the degeneration of retinal ganglion cells, we performed genetic analysis using targeted NGS of 22 already known and candidate genes in a cohort of 1,102 affected individuals. The panel design, library preparation, and sequencing reactions were performed using the Ion AmpliSeq technology. Pathogenic variants were detected in 16 genes in 245 patients (22%), including 186 (17%) and 59 (5%) dominant and recessive cases, respectively. Results confirmed that OPA1 variants are responsible for the majority of dominant IONs, whereas ACO2 and WFS1 variants are also frequently involved in both dominant and recessive forms of ION. All pathogenic variants were found in genes encoding proteins involved in the mitochondrial function, highlighting the importance of mitochondria in the survival of retinal ganglion cells. |
| first_indexed | 2024-12-16T20:30:01Z |
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| id | doaj.art-1ac99f57b91c4a468c90f9bbd54604f7 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-16T20:30:01Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-1ac99f57b91c4a468c90f9bbd54604f72022-12-21T22:17:28ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-03-011210.3389/fneur.2021.602979602979Use of Next-Generation Sequencing for the Molecular Diagnosis of 1,102 Patients With a Autosomal Optic NeuropathyMajida Charif0Majida Charif1Céline Bris2Céline Bris3David Goudenège4David Goudenège5Valérie Desquiret-Dumas6Valérie Desquiret-Dumas7Estelle Colin8Estelle Colin9Alban Ziegler10Alban Ziegler11Vincent Procaccio12Vincent Procaccio13Pascal Reynier14Pascal Reynier15Dominique Bonneau16Dominique Bonneau17Guy Lenaers18Patrizia Amati-Bonneau19Patrizia Amati-Bonneau20University Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceGenetics and Immuno-Cell Therapy Team, Mohammed First University, Oujda, MoroccoUniversity Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceDepartments of Biochemistry and Genetics, University Hospital Angers, Angers, FranceUniversity Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceDepartments of Biochemistry and Genetics, University Hospital Angers, Angers, FranceUniversity Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceDepartments of Biochemistry and Genetics, University Hospital Angers, Angers, FranceUniversity Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceDepartments of Biochemistry and Genetics, University Hospital Angers, Angers, FranceUniversity Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceDepartments of Biochemistry and Genetics, University Hospital Angers, Angers, FranceUniversity Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceDepartments of Biochemistry and Genetics, University Hospital Angers, Angers, FranceUniversity Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceDepartments of Biochemistry and Genetics, University Hospital Angers, Angers, FranceUniversity Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceDepartments of Biochemistry and Genetics, University Hospital Angers, Angers, FranceUniversity Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceUniversity Angers, MitoLab team, UMR CNRS 6015—INSERM U1083, Unité MitoVasc, SFR ICAT, Angers, FranceDepartments of Biochemistry and Genetics, University Hospital Angers, Angers, FranceAdvances in next-generation sequencing (NGS) facilitate the diagnosis of genetic disorders. To evaluate its use for the molecular diagnosis of inherited optic neuropathy (ION), a blinding disease caused by the degeneration of retinal ganglion cells, we performed genetic analysis using targeted NGS of 22 already known and candidate genes in a cohort of 1,102 affected individuals. The panel design, library preparation, and sequencing reactions were performed using the Ion AmpliSeq technology. Pathogenic variants were detected in 16 genes in 245 patients (22%), including 186 (17%) and 59 (5%) dominant and recessive cases, respectively. Results confirmed that OPA1 variants are responsible for the majority of dominant IONs, whereas ACO2 and WFS1 variants are also frequently involved in both dominant and recessive forms of ION. All pathogenic variants were found in genes encoding proteins involved in the mitochondrial function, highlighting the importance of mitochondria in the survival of retinal ganglion cells.https://www.frontiersin.org/articles/10.3389/fneur.2021.602979/fullinherited optic neuropathiesmitochondrial disordersmolecular diagnosisnext generation sequencingretinal ganglia cells |
| spellingShingle | Majida Charif Majida Charif Céline Bris Céline Bris David Goudenège David Goudenège Valérie Desquiret-Dumas Valérie Desquiret-Dumas Estelle Colin Estelle Colin Alban Ziegler Alban Ziegler Vincent Procaccio Vincent Procaccio Pascal Reynier Pascal Reynier Dominique Bonneau Dominique Bonneau Guy Lenaers Patrizia Amati-Bonneau Patrizia Amati-Bonneau Use of Next-Generation Sequencing for the Molecular Diagnosis of 1,102 Patients With a Autosomal Optic Neuropathy Frontiers in Neurology inherited optic neuropathies mitochondrial disorders molecular diagnosis next generation sequencing retinal ganglia cells |
| title | Use of Next-Generation Sequencing for the Molecular Diagnosis of 1,102 Patients With a Autosomal Optic Neuropathy |
| title_full | Use of Next-Generation Sequencing for the Molecular Diagnosis of 1,102 Patients With a Autosomal Optic Neuropathy |
| title_fullStr | Use of Next-Generation Sequencing for the Molecular Diagnosis of 1,102 Patients With a Autosomal Optic Neuropathy |
| title_full_unstemmed | Use of Next-Generation Sequencing for the Molecular Diagnosis of 1,102 Patients With a Autosomal Optic Neuropathy |
| title_short | Use of Next-Generation Sequencing for the Molecular Diagnosis of 1,102 Patients With a Autosomal Optic Neuropathy |
| title_sort | use of next generation sequencing for the molecular diagnosis of 1 102 patients with a autosomal optic neuropathy |
| topic | inherited optic neuropathies mitochondrial disorders molecular diagnosis next generation sequencing retinal ganglia cells |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.602979/full |
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