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Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations
Author(s) -
Ferré Marc,
Bonneau Dominique,
Milea Dan,
Chevrollier Arnaud,
Verny Christophe,
Dollfus Hélène,
Ayuso Carmen,
Defoort Sabine,
Vignal Catherine,
Zanlonghi Xavier,
Charlin JeanFrancois,
Kaplan Josseline,
Odent Sylvie,
Hamel Christian P.,
Procaccio Vincent,
Reynier Pascal,
AmatiBonneau Patrizia
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21025
Subject(s) - optic neuropathy , leber's hereditary optic neuropathy , biology , genetics , mitochondrial dna , atrophy , mutation , locus (genetics) , gene , optic nerve , anatomy
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 e OPA1 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.