Abstract
Mutations in OPA1 are the most frequent cause underlying autosomal dominant optic atrophy (adOA). Until now only few putative splicing mutations in the OPA1 gene have been investigated at the mRNA level and all these result in exon skipping. Here, we report the identification and cDNA analysis of four intronic and three exonic OPA1 gene mutations that cause a variety of splicing defects including activation of cryptic splice sites in either flanking exon or intron sequences, and a leaky splicing mutation. Our results show that cDNA analysis is of prime importance for the full evaluation of the effect of putative splicing mutations in the OPA1 gene.
Reference
Amati-Bonneau P, Pasquier L, Lainey E, Ferre M, Odent S, Malthiery Y, Bonneau D, Reynier P (2005) Sporadic optic atrophy due to synonymous codon change altering mRNA splicing of OPA1. Clin Genet 67:102–103
Baris O, Delettre C, Amati-Bonneau P, Surget MO, Charlin JF, Catier A, Derieux L, Guyomard JL, Dollfus H, Jonveaux P, Ayuso C, Maumenee I, Lorenz B, Mohammed S, Tourmen Y, Bonneau D, Malthiery Y, Hamel C, Reynier P (2003) Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy. Hum Mutat 21:656
Delettre C, Lenaers G, Griffoin JM, Arnaud D, Dollfus H, Kaplan J, Lorenz B, Van de Kamp J, Belenguer P, Hamel CP (2001) Mutation spectrum and splicing variants in the OPA1 gene. Hum Genet 109:548–591
Krawczak M, Reiss J, Cooper DN (1992) The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum Genet 90:41–54
Lorenz B (1994) Hereditary optic atrophy. Ophthalmologe 91:831–850
Pesch UEA, Leo-Kottler B, Mayer S, Jurklies B, Kellner U, Apfelstedt-Sylla E, Zrenner E, Wissinger B (2001) OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance. Hum Mol Genet 10:1359–1368
Rosenberg T, Baumann B, Kohl S, Zrenner E, Jorgensen AL, Wissinger B (2004) Variant phenotypes of incomplete achromatopsia in two cousins with GNAT2 gene mutations. Invest Ophthalmol Vis Sci 45:4256–4262
Thiselton DL, Alexander C, Taanman JW, Brooks S, Rosenberg T, Eiberg H, Andreasson S, Van Regemorter N, Munier FL, Moore AT, Bhattacharya SS, Votruba M (2002) A comprehensive survey of mutations in the OPA1 gene in patients with autosomal dominant optic atrophy. Invest Ophthalmol Vis Sci 43:1715–1724
Acknowledgements
We thank all patients for participation, Drs. Leo-Kottler, Rott, Besch, Kellner, Bertini, Geiger and Janecke for referring patients and Stefanie Bette and Nicole Weisschuh for help and discussions. This work was supported by a grant from the Federal Ministry of Education and Research (Fö. 01KS9602) and the Interdisciplinary Center of Clinical Research Tübingen (IZKF).
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Schimpf, S., Schaich, S. & Wissinger, B. Activation of cryptic splice sites is a frequent splicing defect mechanism caused by mutations in exon and intron sequences of the OPA1 gene. Hum Genet 118, 767–771 (2006). https://doi.org/10.1007/s00439-005-0096-7
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DOI: https://doi.org/10.1007/s00439-005-0096-7