Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.

Farah Ouechtati; Ahlem Merdassi; Yosra Bouyacoub; Leila Largueche; Kaouther Derouiche; Houyem Ouragini; Sonia Nouira; Leila Tiab; Karim Baklouti; Ahmed Rebai; Daniel F Schorderet; Francis L Munier; Leonidas Zografos; Sonia Abdelhak; Leila El Matri

Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.

Farah Ouechtati ^{1, 2} Ahlem Merdassi ² Yosra Bouyacoub ^{1, 2} Leila Largueche ² Kaouther Derouiche ² Houyem Ouragini ¹ Sonia Nouira ¹ Leila Tiab ^{3, 4} Karim Baklouti ² Ahmed Rebai ⁵ Daniel F Schorderet ^{3, 4, 6} Francis L Munier ^{3, 4, 6} Leonidas Zografos ^{4, 6} Sonia Abdelhak ¹ Leila El Matri ²

1 Institut Pasteur de Tunis

2 Oculogenetics Research Unit 17/04

3 Unit of Oculogenomics

4 Swiss Federal Institute of Technology

5 Department of Bioinformatics

6 Eye Hospital, Department of Ophthalmology, Jules-Gonin ,

Abstract : Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations. This retinal disorder is characterized by complete loss of color discrimination due to the absence or alteration of the cones function. The purpose of the present study was the clinical and the genetic characterization of achromatopsia in a large consanguineous Tunisian family. Ophthalmic evaluation included a full clinical examination, color vision testing and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing. A total of 12 individuals were diagnosed with congenital complete achromatopsia. They are members of six nuclear consanguineous families belonging to the same large consanguineous family. Linkage analysis revealed linkage to GNAT2. Mutational screening of GNAT2 revealed three intronic variations c.119-69G>C, c.161+66A>T and c.875-31G>C that co-segregated with a novel mutation p.R313X. An identical GNAT2 haplotype segregating with this mutation was identified, indicating a founder mutation. All patients were homozygous for the p.R313X mutation. This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and the largest family with recessive achromatopsia involving GNAT2; thus, providing a unique opportunity for genotype-phenotype correlation for this extremely rare condition.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Human health and pathology / Infectious diseases

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https://hal-riip.archives-ouvertes.fr/pasteur-00604858
Contributor : Hichem Ben Hassine <>
Submitted on : Wednesday, June 29, 2011 - 6:37:25 PM
Last modification on : Thursday, February 7, 2019 - 2:35:42 PM

Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.

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Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.

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