TY - JOUR
T1 - Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy.
AU - Baris, Olivier
AU - Delettre, Cécile
AU - Amati-Bonneau, Patrizia
AU - Surget, Marie Odile
AU - Charlin, Jean François
AU - Catier, Antoine
AU - Derieux, Laurence
AU - Guyomard, Jean Laurent
AU - Dollfus, Hélène
AU - Jonveaux, Philippe
AU - Ayuso, Carmen
AU - Maumenee, Irene
AU - Lorenz, Birgit
AU - Mohammed, Shehla
AU - Tourmen, Yves
AU - Bonneau, Dominique
AU - Malthièry, Yves
AU - Hamel, Christian
AU - Reynier, Pascal
PY - 2003/6
Y1 - 2003/6
N2 - The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy.
AB - The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy.
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U2 - 10.1002/humu.9152
DO - 10.1002/humu.9152
M3 - Article
C2 - 14961560
AN - SCOPUS:1442307728
SN - 1059-7794
VL - 21
SP - 656
JO - Human mutation
JF - Human mutation
IS - 6
ER -