Mutational analysis of the RB1 gene in Moroccan patients with retinoblastoma

PURPOSE: Retinoblastoma (RB), the most common intraocular tumor occurring in infancy and early childhood, is most often related to mutations in the RB1 gene. In this study, we screened the RB1 germline mutations in 41 unrelated Moroccan patients with retinoblastoma, 25 heritable cases, and 16 sporadic unilateral cases. METHODS: After complete ophthalmic examinations were performed and consent obtained, DNA was extracted from peripheral blood, and screening of RB1 mutations was performed with PCR direct sequencing of the promoter and the 27 coding exons of the RB1 gene. RESULTS: We identified ten germline mutations in 10/41 (24.39%) unrelated patients, among which three had not been previously reported. The mutation detection rate was 40% (10/25) in the heritable cases and 0% (0/16) in the sporadic unilateral cases. Of these mutations, six were nonsense, and three were frameshifts, all associated with severe phenotypes resulting in bilateral and multifocal tumors. One splice site mutation was found in a familial case associated with a low expressivity phenotype resulting in unilateral and unifocal tumors. Moreover, eight intronic variants were identified, three of which were novel. CONCLUSIONS: This first report of RB1 gene screening in Moroccan patients with retinoblastoma shows a comparable mutational spectrum to those reported previously, which has evident importance for managing patients with retinoblastoma and their families

Dossier Contenus Numériques Revue Contrats, Concurrence, Consommation - Contenus Numériques

National audiencele bureau 3A (Loyauté et protection des consommateurs) de la DGCCRF a sollicité Trans Europe Experts pour une expertise sur une série de questions précises juridiques et techniques, se posant dans le cadre des négociations de la proposition de directive concernant les contrats de fourniture de contenu numérique, menées au Conseil de l’Union européenne. L’expertise révèle combien les enjeux de la réglementation des contrats de fourniture de contenu numérique sont fondamentaux. Au croisement du droit des contrats, de la consommation, de la propriété intellectuelle, de la protection des données à caractère personnel, le texte inaugure une nouvelle orientation de la protection du consommateur dans le cadre du marché unique numérique

Dossier Contenus Numériques Revue Contrats, Concurrence, Consommation - Contenus Numériques

National audiencele bureau 3A (Loyauté et protection des consommateurs) de la DGCCRF a sollicité Trans Europe Experts pour une expertise sur une série de questions précises juridiques et techniques, se posant dans le cadre des négociations de la proposition de directive concernant les contrats de fourniture de contenu numérique, menées au Conseil de l’Union européenne. L’expertise révèle combien les enjeux de la réglementation des contrats de fourniture de contenu numérique sont fondamentaux. Au croisement du droit des contrats, de la consommation, de la propriété intellectuelle, de la protection des données à caractère personnel, le texte inaugure une nouvelle orientation de la protection du consommateur dans le cadre du marché unique numérique

Mutations in IMPG1 cause vitelliform macular dystrophies

Vitelliform macular dystrophies (VMD) are inherited retinal dystrophies characterized by yellow, round deposits visible upon fundus examination and encountered in individuals with juvenile Best macular dystrophy (BMD) or adult-onset vitelliform macular dystrophy (AVMD). Although many BMD and some AVMD cases harbor mutations in BEST1 or PRPH2, the underlying genetic cause remains unknown for many affected individuals. In a large family with autosomal-dominant VMD, gene mapping and whole-exome sequencing led to the identification of a c.713T>G (p.Leu238Arg) IMPG1 mutation, which was subsequently found in two other families with autosomal-dominant VMD and the same phenotype. IMPG1 encodes the SPACR protein, a component of the rod and cone photoreceptor extracellular matrix domains. Structural modeling indicates that the p.Leu238Arg substitution destabilizes the conserved SEA1 domain of SPACR. Screening of 144 probands who had various forms of macular dystrophy revealed three other IMPG1 mutations. Two individuals from one family affected by autosomal-recessive VMD were homozygous for the splice-site mutation c.807+1G>T, and two from another family were compound heterozygous for the mutations c.461T>C (p.Leu154Pro) and c.1519C>T (p.A1g507*). Most cases had a normal or moderately decreased electrooculogram Arden ratio. We conclude that IMPG1 mutations cause both autosomal-dominant and -recessive forms of VMD, thus indicating that impairment of the interphotoreceptor matrix might be a general cause of VMD