Alejandro Garanto

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In order to approach the function of the retinal dystrophy CERKL gene we generated a novel knockout mouse model by cre-mediated targeted deletion of the Cerkl first exon and proximal promoter. The excised genomic region (2.3kb) encompassed the first Cerkl exon, upstream sequences including the proximal promoter and the initial segment of the first intron.(More)
PURPOSE Retinitis pigmentosa (RP), a retinal neurodegenerative disorder characterized by apoptosis of photoreceptor cells, is caused by mutations in many different genes. We analyzed the RP gene ceramide kinase-like (CERKL) to determine CERKL function and contribution to pathogenesis. METHODS RT-PCR was performed to characterize CERKL expression in many(More)
PURPOSE To elucidate the functional effect of the ABCA4 variant c.5461-10T→C, one of the most frequent variants associated with Stargardt disease (STGD1). DESIGN Case series. PARTICIPANTS Seventeen persons with STGD1 carrying ABCA4 variants and 1 control participant. METHODS Haplotype analysis of 4 homozygotes and 11 heterozygotes for c.5461-10T→C and(More)
Sumoylation is a reversible post-translational modification that regulates different cellular processes by conjugation/deconjugation of SUMO moieties to target proteins. Most work on the functional relevance of SUMO has focused on cell cycle, DNA repair and cancer in cultured cells, but data on the inter-dependence of separate components of the SUMO pathway(More)
Inherited retinal dystrophies (IRDs) are an extremely heterogeneous group of genetic diseases for which currently no effective treatment strategies exist. Over the last decade, significant progress has been made utilizing gene augmentation therapy for a few genetic subtypes of IRD, although several technical challenges so far prevent a broad clinical(More)
Sphingolipids (SPLs) are finely tuned structural compounds and bioactive molecules involved in membrane fluidity and cellular homeostasis. The core sphingolipid, ceramide (CER), and its derivatives, regulate several crucial processes in neuronal cells, among them cell differentiation, cell-cell interactions, membrane conductance, synaptic transmission, and(More)
Leber congenital amaurosis (LCA) is a severe disorder resulting in visual impairment usually starting in the first year of life. The most frequent genetic cause of LCA is an intronic mutation in CEP290 (c.2991 + 1655A > G) that creates a cryptic splice donor site resulting in the insertion of a pseudoexon (exon X) into CEP290 mRNA. Previously, we showed(More)
Leber congenital amaurosis (LCA) is the most severe form of retinal dystrophy with an onset in the first year of life. The most frequent genetic cause of LCA, accounting for up to 15% of all LCA cases in Europe and North-America, is a mutation (c.2991+1655AG) in intron 26 of CEP290. This mutation generates a cryptic splice donor site resulting in the(More)
Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies that cause visual impairment as a result of photoreceptor cell death. RP is heterogeneous, both clinically and genetically making difficult to establish precise genotype-phenotype correlations. In a Spanish family with autosomal recessive RP (arRP), homozygosity mapping and(More)
PURPOSE To shed light on the pathogenicity of the mutations in the retinitis pigmentosa gene CERKL, the authors aimed to characterize its transcriptional repertoire and focused on the use of distinct promoters and alternative splicing in human and mouse tissues. METHODS In silico genomic and transcriptomic computational customized analysis, combined with(More)