title: Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations.
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.
authors.affiliation: INSERM, U694, Angers, F-49000, France. MaFerre@chu-angers.fr
authors.forename: Marc
authors.initials: M
authors.lastname: Ferré
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Dan
authors.initials: D
authors.lastname: Milea
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chevrollier
authors.forename: Christophe
authors.initials: C
authors.lastname: Verny
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Sabine
authors.initials: S
authors.lastname: Defoort
authors.forename: Catherine
authors.initials: C
authors.lastname: Vignal
authors.forename: Xavier
authors.initials: X
authors.lastname: Zanlonghi
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Charlin
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
authors.forename: Vincent
authors.initials: V
authors.lastname: Procaccio
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
authors.forename: Patrizia
authors.initials: P
authors.lastname: Amati-Bonneau