A high prevalence of biallelic RPE65 mutations in Costa Rican children with Leber congenital amaurosis and early-onset retinal dystrophy.

BACKGROUND: Leber congenital amaurosis (LCA) and early-onset retinal dystrophy (EORD), are primary causes of inherited childhood blindness. Both are autosomal recessive diseases, with mutations in more than 25 genes explaining approximately ~70% of cases. However, the genetic cause for many cases remains unclear. Sequencing studies from genetically isolated populations with increased prevalence of a disorder has proven useful for rare variant studies, making Costa Rica an ideal place to study LCA/EORD genetics. MATERIALS AND METHODS: Twenty-eight affected children (25 LCA, three EORD) and their immediate family members, totaling 52 individuals (30 affected) from 22 families, were sequenced. Whole exome sequencing was performed on all affected individuals. Available parents were analyzed either by whole exome sequencing (WES) or Sanger sequencing to determine transmission. RESULTS: All affected individuals demonstrated compound heterozygous or homozygous mutations in known Inherited Retinal Disease (IRD) associated genes. Twelve variants were identified in at least one individual in three genes, RDH12, RPE65, and USH2A. Four recurrent RPE65 mutations were observed in 97% of individuals and 95% of families. All patients with LCA and two of the three individuals with EORD had biallelic mutations in RPE65; one child with EORD had a homozygous RDH12 mutation. CONCLUSIONS: These data suggest that the majority of LCA/EORD in Costa Rica is due to four founder mutations in RPE65 which have been maintained in this genetically isolated population. This finding is of great clinical significance due to the availability of gene therapy recently approved in the US and European Union for patients with biallelic RPE65 defects.

Effectiveness of the GoCheck Kids Vision Screener in Detecting Amblyopia Risk Factors.

PURPOSE: The GoCheck Kids smartphone photoscreening app (Gobiquity Mobile Health, Scottsdale, Arizona, USA), introduced in 2014, is marketed to pediatricians with little published validation. We wished to evaluate the GoCheck Kids Screener for accuracy in detecting amblyopia risk factors (ARF) using 2013 American Association for Pediatric Ophthalmology and Strabismus guidelines. DESIGN: Validity assessment. METHODS: Children 6 months to 6 years of age presenting from October 2016 to August 2017 were included. Children were screened with the GoCheck preloaded Nokia Lumia 1020, software version 4.6 with image processing version R4d, prior to undergoing a comprehensive eye examination by a pediatric ophthalmologist masked to the screener results. Determination of the presence of age-specific ARF was made based upon the examination and compared with the GoCheck recommendation. RESULTS: A total of 206 children were included (average age 43 months). When compared to examination, GoCheck had a sensitivity of 76.0% and specificity of 67.2% in detecting ARF. Positive predictive value was 57.0% and negative predictive value 83.0%. The screener results of 13 children were changed from "no risk factors" to "risk factors identified" based on the GoCheck remote review process. Four images remained "not gradable" and screening was unsuccessful in 3 children. CONCLUSION: In our high-risk population, this version of the Gocheck Kids smartphone app was useful in identifying ARF in children who are often not able to cooperate with visual acuity testing. This study informs pediatricians about the efficacy of this new screener as they make decisions about how to best detect vision problems in young children.