Purchase this article with an account.
Blanca C. Flores, Cristina Villanueva-Mendoza, Irma Lopez, Robert K. Koenecoop; Molecular characterization in Mexican patients with Leber Congenital Amaurosis and Early Onset Retinal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5394.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To identify the causal genes in Mexican patients with Leber Congenital Amaurosis (LCA) and Early Onset Retinal Dystrophy (EORD). Leber Congenital Amaurosis is one of the most severe inherited retinal dystrophies with the earliest age of onset. Sixteen genes are known to be associated with LCA. These genes are also sometimes related with EORD and autosomal recessive Retinitis Pigmentosa (RP).
A systemic and ophthalmologic evaluation for phenotypic characterization was done including visual acuity, refraction, slit-lamp biomicroscopy, fundus photography and electroretinogram (ERG). Known LCA mutations were excluded using APEX technology. We performed homozygosity mapping using Illumina Infinium HD to identify homozygous regions. Regions of interest were analyzed using the Illumina Bead Studio and P-link software. Positional candidate genes were identified using the USCS human genome browser. Bioinformatics, gene ontology, interpro domain comparisons and gene expression profiling were performed to identify and rank candidate genes.
Affected LCA patients had best-corrected visual acuities that ranged from no light perception to 20/250, nystagmus and posterior segment changes such as pigmentary retinopathy, vascular thining and a pale retina or optic disc. ERG evidenced undetectable response when available. The EORD patients had nyctalopia, visual acuity of 10/60, atrophic changes in macula, pale retina and undetectable response in ERG. We identified 8 homozygous regions where at least 5 patients overlap, none containing known LCA or RP genes. These homozygous regions range from 0.5 to 1.5 Mb. The largest interval resides on chromosome 1. The second largest region is on chromosome 20.
We describe the phenotype of Mexican patients that appear to have a unique form of retinal distrophy and we identified novel intervals which do not overlap with known retinal dystrophy loci or genes. Finding this gene will improve our understanding of both photoreceptor death and health. Funding: APEC, Mexico, CIHR, FFB-Canada, FRSQ, Reseau Vision.
This PDF is available to Subscribers Only