April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Novel Cone Transducin Alpha Subunit Mutation In Tunisian Patients And Genotype-phenotype Correlation In Complete Achromatopsia
Author Affiliations & Notes
  • Farah Ouechtati
    Oculogenetics UR17/03, Institute of Ophthalmology of Tunis, Tunis, Tunisia
    Molecular Investigation of Genetic Orphan Diseases UR04/SP03, Institut Pasteur de Tunis, Tunis, Tunisia
  • Ahlem Merdassi
    Oculogenetics UR17/03, Institute of Ophthalmology of Tunis, Tunis, Tunisia
  • Yosra Bouyacoub
    Oculogenetics UR17/03, Institute of Ophthalmology of Tunis, Tunis, Tunisia
    Molecular Investigation of Genetic Orphan Diseases UR04/SP03, Institut Pasteur de Tunis, Tunis, Tunisia
  • Leila Largueche
    Oculogenetics UR17/03, Institute of Ophthalmology of Tunis, Tunis, Tunisia
  • Leila Tiab
    Oculogenomics laboratory, Institute for Research in Ophthalmology and the Swiss Federal Institute of Technology, Sion, Switzerland
  • Daniel F. Schorderet
    Oculogenomics laboratory, Institute for Research in Ophthalmology and the Swiss Federal Institute of Technology, Sion, Switzerland
    Department of Ophthalmology, Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
  • Francis L. Munier
    Oculogenomics laboratory, Institute for Research in Ophthalmology and the Swiss Federal Institute of Technology, Sion, Switzerland
    Department of Ophthalmology, Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
  • Leonidas Zografos
    Oculogenomics laboratory, Institute for Research in Ophthalmology and the Swiss Federal Institute of Technology, Sion, Switzerland
    Department of Ophthalmology, Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
  • Sonia Abdelhak
    Molecular Investigation of Genetic Orphan Diseases UR04/SP03, Institut Pasteur de Tunis, Tunis, Tunisia
  • Leila El Matri
    Oculogenetics UR17/03, Institute of Ophthalmology of Tunis, Tunis, Tunisia
  • Footnotes
    Commercial Relationships  Farah Ouechtati, None; Ahlem Merdassi, None; Yosra Bouyacoub, None; Leila Largueche, None; Leila Tiab, None; Daniel F. Schorderet, None; Francis L. Munier, None; Leonidas Zografos, None; Sonia Abdelhak, None; Leila El Matri, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2376. doi:
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      Farah Ouechtati, Ahlem Merdassi, Yosra Bouyacoub, Leila Largueche, Leila Tiab, Daniel F. Schorderet, Francis L. Munier, Leonidas Zografos, Sonia Abdelhak, Leila El Matri; Novel Cone Transducin Alpha Subunit Mutation In Tunisian Patients And Genotype-phenotype Correlation In Complete Achromatopsia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2376.

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Abstract

Purpose: : Complete achromatopsia is a rare autosomal recessive disease due to CNGA3, CNGB3, GNAT2 and PDE6C mutations. We studied a large consanguineous Tunisian family including twelve individuals.

Methods: : Ophthalmic evaluation included a full clinical examination, color vision testing, optical coherence tomography and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing.

Results: : In all affected subjects, acuity ranged from 20/50 to 20/200. Fundus examination was normal except for two patients who had respectively 4 mm and 5 mm diameters of peripheral congenital hypertrophy. Likewise retinal layers exploration by OCT revealed no change in the thickness of the central retina. Color Vision with 100 Hue Farnsworth test described a profound color impairment along all three axes of color vision. The haplotype analysis of GNAT2 markers revealed that all affected offspring were homozygous by descent for the four polymorphic markers. The maximum lod score value, 4.33, confirmed the evidence for linkage to the GNAT2 gene.A homozygous novel nonsense mutation R313X was identified segregating with an identical GNAT2 haplotype in all affected subjects. This mutation could interrupt interaction with photoactivated rhodopsin, resulting in a failure of visual transduction. In fact, ERG showed a clearly abolished photopic b-wave and flicker responses with no residual cone function justifying the severe GNAT2 achromatopsia phenotype.

Conclusions: : This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and of the largest family with recessive achromatopsia involving GNAT2, thus providing a unique opportunity for genotype phenotype correlation for this extremely rare condition.

Keywords: genetics • retinal degenerations: hereditary • color vision 
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