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Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations |
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| Authors: | Marc Ferré Dominique Bonneau Dan Milea Arnaud Chevrollier Christophe Verny Hélène Dollfus Carmen Ayuso Sabine Defoort Catherine Vignal Xavier Zanlonghi Jean‐Francois Charlin Josseline Kaplan Sylvie Odent Christian P. Hamel Vincent Procaccio Pascal Reynier Patrizia Amati‐Bonneau |
| Affiliation: | 1. INSERM, U694, Angers, F‐49000, France;2. Université d'Angers, Faculté de Médecine, Angers, F‐49000, France;3. CHU d'Angers, Département de Biochimie et Génétique, Angers, F‐49000, France;4. Glostrup Hospital, Department of Ophthalmology, Glostrup, DK‐2600, Denmark;5. University of Copenhagen, Copenhagen, DK‐1165, Denmark;6. CHU d'Angers, Département de Neurologie, Angers, F‐49000, France;7. INSERM, Equipe Avenir 3439, Strasbourg, F‐67000, France;8. Université Louis Pasteur‐Strasbourg, Faculté de Médecine, Laboratoire de Génétique Médicale, Strasbourg, F‐67000, France;9. CHRU de Strasbourg, Service de Génétique Médicale, Strasbourg, F‐67000, France;10. Fundación Jiménez Díaz, Servicio de Genética, CIBERER, Madrid, Spain;11. CNRS, UMR 8160, Lille, F‐59000, France;12. Université de Lille 2, Lille, F‐59000, France;13. CHRU de Lille, H?pital Roger Salengro, Service d'Explorations Fonctionnelles de la Vision, Lille, F‐59000, France;14. Fondation Rothschild, Département d'Ophtalmologie, Paris, F‐75019, France;15. Clinique Sourdille, Laboratoire d'Explorations Fonctionnelles de la Vision, Nantes, F‐44000, France;16. Université de Rennes 1, Faculté de Médecine, Rennes, F‐35000, France;17. CHU de Rennes, Service d'Ophtalmologie, Rennes, F‐35000, France;18. INSERM, U781, Unité de Recherches Génétique et Epigénétique des Maladies Métaboliques, Neurosensorielles et du Développement, Paris, F‐75014, France;19. Université Paris Descartes, Faculté de Médecine, Paris, F‐75014, France;20. AP‐HP, Groupe Hospitalier Necker, Service de Génétique Médicale, Paris, F‐75014, France;21. CHU de Rennes, Département de Médecine de l'Enfant et de l'Adolescent, Rennes, F‐35000, France;22. CHRU de Montpellier, Montpellier, F‐34000, France;23. Université Montpellier1 et Montpellier2, Institut des Neurosciences, Montpellier, F‐34000, France;24. CNRS, UMR6214, F‐49000 Angers, France;25. INSERM, U771, F‐49000 Angers, France |
| Abstract: | We report the results of molecular screening in 980 patients carried out as part of their work‐up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten primary LHON‐causing mtDNA mutations and examining the entire coding sequences of the OPA1 and OPA3 genes, the two genes currently identified in ADOA. Molecular defects were identified in 440 patients (45% of screened patients). Among these, 295 patients (67%) had an OPA1 mutation, 131 patients (30%) had an mtDNA mutation, and 14 patients (3%), belonging to three unrelated families, had an OPA3 mutation. Interestingly, OPA1 mutations were found in 157 (40%) of the 392 apparently sporadic cases of optic atrophy. The eOPA1 locus‐specific database now contains a total of 204 OPA1 mutations, including 77 novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work‐up of optic neuropathies. Our results highlight the importance of investigating LHON‐causing mtDNA mutations as well as OPA1 and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease. © 2009 Wiley‐Liss, Inc. |
| Keywords: | hereditary optic atrophy mitochondria autosomal dominant optic atrophy ADOA optic atrophy 1 OPA1 Leber's hereditary optic atrophy LHON optic atrophy 3 OPA3 |