TY - JOUR
T1 - Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations
AU - Ferré, Marc
AU - Bonneau, Dominique
AU - Milea, Dan
AU - Chevrollier, Arnaud
AU - Verny, Christophe
AU - Dollfus, Hélène
AU - Ayuso, Carmen
AU - Defoort, Sabine
AU - Vignal, Catherine
AU - Zanlonghi, Xavier
AU - Charlin, Jean-Francois
AU - Kaplan, Josseline
AU - Odent, Sylvie
AU - Hamel, Christian P
AU - Procaccio, Vincent
AU - Reynier, Pascal
AU - Amati-Bonneau, Patrizia
AU - Ferré, Marc
AU - Bonneau, Dominique
AU - Milea, Dan
AU - Chevrollier, Arnaud
AU - Verny, Christophe
AU - Dollfus, Hélène
AU - Ayuso, Carmen
AU - Defoort, Sabine
AU - Vignal, Catherine
AU - Zanlonghi, Xavier
AU - Charlin, Jean-Francois
AU - Kaplan, Josseline
AU - Odent, Sylvie
AU - Hamel, Christian P
AU - Procaccio, Vincent
AU - Reynier, Pascal
AU - Amati-Bonneau, Patrizia
N1 - Keywords: DNA, Mitochondrial; GTP Phosphohydrolases; Genetic Testing; Humans; Mutation; Optic Atrophies, Hereditary; Optic Atrophy, Autosomal Dominant; Optic Atrophy, Hereditary, Leber; Proteins
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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.
AB - 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.
U2 - 10.1002/humu.21025
DO - 10.1002/humu.21025
M3 - Journal article
C2 - 19319978
SN - 1059-7794
VL - 30
SP - E692-705
JO - Human Mutation
JF - Human Mutation
IS - 7
ER -