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