LCA5, a rare subset of Leber congenital amaurosis, is a retinal dystrophy characterized by loss in visual acuity, hyperopia and pendular nystagmus. Patients often display Franceschetti's oculo-digital sign, a behavior involving repeatedly pressing or rubbing the eyes with the fingers. Apart from the pigmentary retinopathy, fundus atrophy and colobomatous appearance associated with retinal dystrophy, patients also exhibit a markedly reduced response to electrophysiological stimulation. Unlike other types of LCA, this condition is not associated with multi-system abnormalities. Patients that have been studied thus far have shown normal neurologic, hepatic and renal function. The disorder has an early-infantile onset and is progressive in nature, resulting in complete vision loss over time. LCA has an overall incidence of about 2-3 cases per 100,000 individuals, making it one of the most common causes of blindness in children. However, LCA5 is a rare condition with only a handful of cases reported worldwide.
The disorder is diagnosed based on ophthalmological examinations and molecular analysis of the LCA5 gene. There is currently no cure for LCA and treatment remains supportive and symptomatic. Patients benefit from correction for refractive error and low-vision aids. Periodic assessment for the presence of amblyopia, glaucoma, or cataract is encouraged.
LCA5 follows an autosomal recessive pattern of inheritance and is caused by homozygous mutations in the LCA5 gene. This gene encodes lebercilin, a protein believed to play a role in minus end-directed microtubule transport as well as in centrosomal and ciliary functions. Mutations in this gene associated with LCA5 include deletions, duplications and transitions, which result in frameshifts and premature truncation.
Monies et al. (2017) illustrated the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 3-year-old male, suffered from an atrial septal defect, failure to thrive, growth retardation, fine/gross motor delay, speech delay, learning disability, stereotypic behaviors, cleft lip, blindness and congenital heart disease. Using whole exome sequencing, a homozygous mutation (c.763C>T, p.R255X) was identified in exon 4 of the patient’s LCA5 gene. This mutation explained the LCA phenotype, while the remaining congenital anomalies were attributed to an additional unidentified variant.
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