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

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.

Identification of three Sorex species with microsatellite markers

Three sibling species of shrews, the common shrew (Sorex araneus), the Valais shrew (S. antinorii) and the Jersey shrew (S. coronatus) are morphologically similar. Different techniques based on karyorypes, morphology, biochemistry and genetic markers have been developed to identify individuals from these taxa. In this paper, we have used multiple microsatellite markers (L13, L14 and L99) to identify 55 dead animals coming from the Tarentaise Valley in France. As some individuals showed an unclear pattern with loci previously thought to be diagnostic (Lugon-Moulin et al. 2000), we have used morphologic measurements (Hausser et al. 1991) to confirm the status of these animals. This analysis clearly showed the limitations of the use of genetic diagnostic markers that have been designed in local populations and then applied to a wider scale. Even if these markers have great advantages over other techniques (i.e. simple to use and do not require samples from living animals), they should always be used with caution. There is always a risk of a locus not being diagnostic in the sampling region or in finding individuals with hybrid genotypes. Additional genetic markers should then be used, simultaneously with other identification techniques, to be sure of the status of the individuals.