Expanding the Clinical and Molecular Heterogeneity of Nonsyndromic Inherited Retinal Dystrophies

A New Cerkl Mouse Model Generated by CRISPR-Cas9 Shows Progressive Retinal Degeneration and Altered Morphological and Electrophysiological Phenotype

“…Further work on the effect of reported mutations on the function of different CERKL isoforms may explain why in some patients the phenotypic traits are clinically associated with RP or CRD, which differ in whether rods (peripheral retina) or cones (macula) are first affected, respectively (see Supplementary Table S2 for a complete list of CERKL mutations and reported retinal phenotypes in human patients). However, genotype–phenotype correlation in human patients may be particularly difficult for CERKL , as the same pathogenic mutation in homozygosis can cause either autosomal recessive RP with high macular affectation 25 or autosomal recessive CRD, 7 , 32 not only in different families but also in sibling patients within the same family, 33 the main conclusion being that CERKL function is relevant for both types of photoreceptors. Also, the severity of retinopathy and visual loss in humans differ even in homozygous patients of the same family.…”

Management of retinitis pigmentosa by Wharton’s jelly-derived mesenchymal stem cells: prospective analysis of 1-year results

“…Genetic mutations that lead to retinitis pigmentosa can occur or be transferred by autosomal dominant (AD), autosomal recessive (AR), X-linked, mitochondrial, mosaic, or sporadic inheritance [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Rhodopsin and opsin are the major protein products which synthesized in the photoreceptors [18][19][20].…”

“…Rhodopsin and opsin are the major protein products which synthesized in the photoreceptors [18][19][20]. Photoreceptors also need lipoproteins and glycoproteins, which are part of the disc membranes for the transfer of functional proteins involved in the visual cycle [13][14][15]. The inner and outer segments of the photoreceptors are interconnected by cilia that have a microtubule structure.…”

“…Since both alleles are mutants, they progress faster. The average annual EZ loss rate is around 10% [11][12][13][14][15][16][17]. The proteins responsible for the energy cycle are similar to the exosome contents produced by stem cells .…”

“…Today, 260 different mutations detected in these 90 genes have been shown to lead to RP [9,10]. Retinitis pigmentosa is a rare and very heterogeneous disease [11][12][13][14][15][16][17][18][19][20][21][22]. For this reason, gene therapy has many unknowns and is not cost-effective [10,23].…”