Human Genetics

, Volume 109, Issue 6, pp 584–591

Mutation spectrum and splicing variants in the OPA1 gene

  • Cécile Delettre
  • Jean-Michel Griffoin
  • Josseline Kaplan
  • Hélène Dollfus
  • Birgit Lorenz
  • Laurence Faivre
  • Guy Lenaers
  • Pascale Belenguer
  • Christian P. Hamel
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
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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

Authors and Affiliations

  • Cécile Delettre
    • 1
  • Jean-Michel Griffoin
    • 1
  • Josseline Kaplan
    • 2
  • Hélène Dollfus
    • 3
  • Birgit Lorenz
    • 4
  • Laurence Faivre
    • 5
  • Guy Lenaers
    • 6
  • Pascale Belenguer
    • 6
  • Christian P. Hamel
    • 1
  1. 1.Inserm U. 254, 71, rue de Navacelles, 34090 Montpellier, FranceFrance
  2. 2.Inserm U. 393, Handicaps génétiques de l'enfant, Hôpital Necker-Enfants malades, 149, rue de Sèvres, 75743 Paris cedex 15, FranceFrance
  3. 3.Service de Génétique Médicale, Hôpital de Hautepierre, Avenue Molière, 67098 Strasbourg, FranceFrance
  4. 4.Kinderophthalmologie, Augenklinikum der Universität, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, GermanyGermany
  5. 5.Centre de Génétique, Hôpital d'Enfants, 10, Boulevard Maréchal de Lattre de Tassigny, 21034 Dijon, FranceFrance
  6. 6.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, FranceFrance