Poster 203

by in  Poster Session 3

Genetic Analysis of Children with Hereditary Retinal Dystrophy within the National Health Care System of Costa Rica

Joaquin Martinez, MD; Ramses Badilla, MD; W. Bailey Glen, PhD; Daynna J. Wolff, PhD, FACMG; Millicent W. Peterseim, MD
Storm Eye Institute/Medical University of South Carolina and National Children’s Hospital of Costa Rica
Charleston SC USA and San Jose Costa Rica


Introduction: Hereditary retinal dystrophy has been reported a significant cause of poor childhood vision in Latin America (1,2). Given centralized Costa Rica healthcare,  children are followed at the pediatric retina clinic of the National Children’s Hospital, allowing detailed and longitudinal phenotypic data to be obtained.  Our study identifies genetic variants in this unique population.

Methods: DNA was analyzed from 32 individuals from 18 different families with Leber’s congenital amaurosis (LCA) or retinitis pigmentosa. Single nucleotide genotyping arrays were performed on probands to detect copy number variants/regions of homozygosity that demonstrated identity by descent. Whole exome sequencing identified single basepair mutations and small insertions/deletions. All patients received complete ophthalmologic examination, fundus photography, and ERG.

Results: Probands, mean age 8.7 years (range 4-16), demonstrated poor vision in infancy and flat or diminished ERG, with minimal variability. Given clinical findings, twelve of the children were diagnosed with LCA. Microarray detected a median 5% homozygosity with many known recessive retinal dystrophy genes mapping within homozygous regions. Of the 26 affected individuals analyzed, 22 (85%) demonstrated biallelic mutations in RPE65 predicted to be disease-causing. Three other affected probands demonstrated assumed biallelic loss in ADMATS18, NYX-1 and RDH12, and the fourth individual had an X chromosome deletion involving OPN1LW and  OPN1MW and a mutation in NYX1.

Discussion: We find a very high prevalence of biallelic RPE65 mutations in LCA Costa Rican children, likely arising from founder effects.

Conclusion: We report the first genetic analysis of children with hereditary retinal disease in Costa Rica, perhaps allowing hope for future therapy (3).

References: 1) Furtado JM, Lansingh VC, Carter MJ, Milanese MF, Pena BN, Ghersi HA, Bote PL, Nano ME, Silva JC. Causes of Blindness and Visual Impairment in Latin America. Seddon J and Fong D, editors of Public Health and the Eye. Surv of Ophthalmol 2012; 56(2):149-176.
2) Gilbert CE, Canovas R, Kocksch de Canovas R, Foster A. Causes of blindness and severe visual impairment in children in Chile. Dev Med Child Neurol. 1994;36:326-33.
3)  Coussa RG, Solache IL, Koenekoop RK. Leber congenital amaurosis, from darkness to light: An ode to Irene Maumenee, Ophthalmic Genetics, 38:1, 7-15, 2017.

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