Disease relevance of LCA5

• Progression of phenotype in Leber's congenital amaurosis with a mutation at the LCA5 locus [1].
• Simultaneous screening for all known LCA-associated variants in large LCA cohorts allows systematic detection and analysis of genetic variation, facilitating prospective diagnosis and ultimately predicting disease progression [2].
• The first one includes patients whose symptoms fit the traditional definition of LCA, i.e., congenital or very early cone-rod dystrophy, while the second group gathers patients affected with severe yet progressive rod-cone dystrophy [3].
• Overall, our cohort of LCA carriers did not describe significant subjective visual difficulties, including nyctalopia and/or photosensitivity [4].
• Macular coloboma-type LCA shows genetic heterogeneity and it is not possible to establish a phenotype-genotype correlation with LCA5 and macular coloboma [5].

Psychiatry related information on LCA5

• New autosomal-recessive syndrome of Leber congenital amaurosis, short stature, growth hormone insufficiency, mental retardation, hepatic dysfunction, and metabolic acidosis [6].

High impact information on LCA5

• Mutations in the human RPE65 gene cause a blinding disease of infancy called Leber congenital amaurosis [7].
• Here we study one of the most clinically severe retinal degenerations, Leber congenital amaurosis (LCA) [8].
• De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis [9].
• The most severe cases are termed Leber congenital amaurosis (LCA), while the less aggressive forms are usually considered juvenile retinitis pigmentosa [10].
• Recently, mutations in the retinal-specific guanylate cyclase gene were found in patients with LCA [10].

Biological context of LCA5

• The ocular findings and the evolution of the macula staphyloma are described in five members of a Pakistani family with consanguinity and a mutation in the LCA5 gene [1].
• Molecular genetics of Leber congenital amaurosis [11].
• CONCLUSIONS: The variation of phenotypic expression in carriers among 5 LCA genotypes indicates that there is considerable phenotypic overlap [4].
• Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis [3].
• RESULTS: In haplotype analysis, no linkage to LCA5 or GUCY2D loci was detected [5].

Anatomical context of LCA5

• To map the disease loci several Pakistani families suffering from autosomal recessive retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium and Leber congenital amaurosis (LCA) were analyzed [12].
• Our studies may provide clues for mechanisms of photoreceptor degeneration in RP12 and LCA [13].
• LCA is characterized by an extinguished electroretinogram in infancy, which is thought to be indicative of an early and severe impairment of both the rod and cone photoreceptors in the human retina [14].
• The Leber congenital amaurosis gene product AIPL1 is localized exclusively in rod photoreceptors of the adult human retina [14].
• CONCLUSIONS: An 11-year-old subject with LCA caused by mutant GUCY2D had only light perception but retained substantial numbers of cones and rods in the macula and far periphery [15].

Associations of LCA5 with chemical compounds

• Mutations in RPE65, a gene essential to normal operation of the visual (retinoid) cycle, cause the childhood blindness known as Leber congenital amaurosis (LCA) [16].
• Most LCA-associated missense mutations in RPGRIP1 are located in a segment that encodes two C2 domains [17].
• Vitamin A deficiency and genetically inherited diseases, such as some forms of retinitis pigmentosa and Leber congenital amaurosis, appear to kill like this: transduction is activated at a high rate and continuously, and this causes the rods to die [18].

Regulatory relationships of LCA5

• Mutation screening of patients with Leber Congenital Amaurosis or the enhanced S-Cone Syndrome reveals a lack of sequence variations in the NRL gene [19].

Other interactions of LCA5

• A genome-wide screen for homozygosity was conducted in a large consanguineous family originating from Palestine, for which no mutation was found in any of the six known LCA genes and that excluded the LCA3 and LCA5 loci [20].
• The resultant LCA array allows simultaneous detection of all known disease-associated alleles in any patient with early-onset RP [2].
• Pathogenic GUCY2D mutations result in the most severe form of LCA [21].
• Mutations in CRB1, and to a lesser extent, in GUCY2D, underlie most LCA cases in this cohort [21].
• Complete exon-intron structure of the RPGR-interacting protein (RPGRIP1) gene allows the identification of mutations underlying Leber congenital amaurosis [22].

Analytical, diagnostic and therapeutic context of LCA5

• Animal models of Leber congenital amaurosis have greatly added to understanding the impact of the genetic defects on retinal cell death, and response to rescue [23].
• Longitudinal studies of visual performance show that most Leber congenital amaurosis patients remain stable, some deteriorate, and rare cases exhibit improvements [23].
• Retinal gene therapy restores vision to blind canine and murine models of LCA [16].
• These results are promising for future clinical trials of human patients with retinal degenerative diseases, such as Leber congenital amaurosis, that result from RPE65 gene defects [24].
• The virtual lack of peroxisomes in a liver biopsy specimen lends further support to the contention that at least some patients with Leber congenital amaurosis may have one of the recently defined "peroxisomal disorders." The biochemical findings indicate the possibility of prenatal diagnosis [25].

References