Human Genetics

, Volume 109, Issue 6, pp 584–591

Mutation spectrum and splicing variants in the OPA1 gene

Authors

  • Cécile Delettre
    • Inserm U. 254, 71, rue de Navacelles, 34090 Montpellier, France
  • Jean-Michel Griffoin
    • Inserm U. 254, 71, rue de Navacelles, 34090 Montpellier, France
  • Josseline Kaplan
    • Inserm U. 393, Handicaps génétiques de l'enfant, Hôpital Necker-Enfants malades, 149, rue de Sèvres, 75743 Paris cedex 15, France
  • Hélène Dollfus
    • Service de Génétique Médicale, Hôpital de Hautepierre, Avenue Molière, 67098 Strasbourg, France
  • Birgit Lorenz
    • Kinderophthalmologie, Augenklinikum der Universität, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
  • Laurence Faivre
    • Centre de Génétique, Hôpital d'Enfants, 10, Boulevard Maréchal de Lattre de Tassigny, 21034 Dijon, France
  • Guy Lenaers
    • CNRS UMR 5088, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération, Université Paul Sabatier, Bâtiment IVR3-B1, 118, route de Narbonne, 31062 Toulouse cedex 4, France
  • Pascale Belenguer
    • CNRS UMR 5088, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération, Université Paul Sabatier, Bâtiment IVR3-B1, 118, route de Narbonne, 31062 Toulouse cedex 4, France
  • Christian P. Hamel
    • Inserm U. 254, 71, rue de Navacelles, 34090 Montpellier, France
Original Investigation

DOI: 10.1007/s00439-001-0633-y

Cite this article as:
Delettre, C., Griffoin, J., Kaplan, J. et al. Hum Genet (2001) 109: 584. doi:10.1007/s00439-001-0633-y

Abstract.

Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy that features low visual acuity leading in many cases to legal blindness. We have recently shown, with others, that mutations in the OPA1 gene encoding a dynamin-related mitochondrial protein, underlie the dominant form of optic atrophy. Here we report that OPA1 has eight mRNA isoforms as a result of the alternative splicing of exon 4 and two novel exons named 4b and 5b. In addition, we screened a cohort of 19 unrelated patients with dominant optic atrophy by direct sequencing of the 30 OPA1 exons (including exons 4b and 5b) and found mutations in 17 (89%) of them of which 8 were novel. A majority of these mutations were truncative (65%) and located in exons 8 to 28, but a number of them were amino acid changes predominantly found in the GTPase domain (exons 8 to 15). We hypothesize that at least two modifications of OPA1 may lead to dominant optic atrophy, that is alteration in GTPase activity and loss of the last seven C-terminal amino acids that putatively interact with other proteins.

Copyright information

© Springer-Verlag 2001