Leber congenital amaurosis and early onset severe retinal dystrophy in the Czech Republic: Mutational spectrum and clinical findings

Abstract

AbstractPurpose: Leber congenital amaurosis (LCA)/early onset severe retinal dystrophy (EOSRD) is a group of ultra‐rare retinal diseases with an estimated prevalence of 1/80 000. The aim of this study was to perform a detailed clinical characterization in patients with LCA/EOSRD confirmed at the DNA level.Materials and methods: 16 patients (eight females, eight males) from 16 families underwent ocular examination in the Department of Ophthalmology, 1st Faculty of Medicine and General University Hospital in Prague between the years 2010–2021. Pathogenic variants in genes associated with LCA/EOSRD were searched using targeted gene panels, exome and/or genome sequencing. Confirmation of the presence of causal variants and segregation within the families was performed by Sanger sequencing. Next we have performed review of available clinical documentation of five additional probands examined elsewhere in the Czech Republic.Results. The mean age at the first examination was 17.8 years (range 2–42 years). The mean age of symptoms onset was 1,99 years (range 6 weeks to 5 years). In five patients, the disease was caused by biallelic mutations in the RPE65 gene, in 4 patients in the CEP290 gene and in three patients in the CRB1 gene. Biallelic mutations in the GUCY2D, LCA5, RPGRIP1 and CLN3 genes were the cause of the disease in one patient each. As for probands suffering from LCA/EOSRD and examined elsewhere two were documented carriers for pathogenic variants in the CEP290 gene, two in the CRB1 gene and one in the GUCY2D gene.Conclusions: This is the first study presenting molecular genetic and clinical characteristics of patients with LCA/EOSRD from the Czech Republic. Biallelic mutations in the CEP290 gene are the most common genetic cause of LCA/EOSRD in our patient group.This work was supported by NU20‐07‐00182; EJPRD19‐234 Solve‐RET.