Abstrakt
Introduction: Congenital and juvenile cataracts are phenotypically and genetically very heterogeneous group. In this study, we aimed to investigate the molecular genetic cause in Czech patients with bilateral congenital or juvenile cataracts not associated with other ocular or systemic clinical findings.
Materials and Methods: Whole exome sequencing was performed in 10 probands of Czech origin. Variants with minor allele frequency less than 0.005 as per GnomAD v.2 were filtered and those located in genes known to be associated with cataract development as per Cat-Map database were given a priority for further evaluation. Conventional sequencing was used to follow segregation of the presumably pathogenic variants in available first degree relatives.
Results: Out of the 10 probands 6 had a family history of congenital or infantile cataracts. In total 5 variants classified as pathogenic or likely pathogenic as per American College of Medical Genetics and Genomics guidelines were identified. Two variants were novel; c.299T>A in GJA3 (NM_021954) and c.2665G>A in EPHA2 (NM_001329090). No pathogenic variants were found in 5 probands.
Conclusions: Herein we report for the first time mutational spectrum of non-syndromic cataracts in Czech patient population. The failure to identify disease-causing variants in half of the analysed cases suggests, that either the underlying mechanisms are not of genetic origin and/or that the pathogenic changes are not located in coding regions of the genome. Only two probands with family history of cataracts remained unsolved. Alternatively, larger structural variants or rearrangement could be also implicated.
Supported by AZV 17-30500A.