Glen, W. Bailey Peterseim, M. Millicent W. Badilla, Ramses Znoyko, Iya Bourg, Andre Wilson, Robert Hardiman, Gary Wolff, Daynna Martinez, Joaquin A high prevalence of biallelic <i>RPE65</i> mutations in Costa Rican children with Leber congenital amaurosis and early-onset retinal dystrophy <p><b>Background</b>: 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.</p> <p><b>Materials and Methods</b>: 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.</p> <p><b>Results</b>: 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, <i>RDH12, RPE65</i>, and <i>USH2A</i>. Four recurrent <i>RPE65</i> 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 <i>RPE65</i>; one child with EORD had a homozygous <i>RDH12</i> mutation.</p> <p><b>Conclusions</b>: These data suggest that the majority of LCA/EORD in Costa Rica is due to four founder mutations in <i>RPE65</i> 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 <i>RPE65</i> defects.</p> RPE65;Costa Rica;Leber congenital amaurosis;inherited retinal disease 2019-03-14
    https://tandf.figshare.com/articles/journal_contribution/A_high_prevalence_of_biallelic_i_RPE65_i_mutations_in_Costa_Rican_children_with_Leber_congenital_amaurosis_and_early-onset_retinal_dystrophy/7848020
10.6084/m9.figshare.7848020.v1