Gene Panel Analysis Reveals Overlapping Genetic Causes of Inherited Cataracts and Other Ocular Phenotypes in...

Inherited forms of cataract are a clinically important and genetically heterogeneous cause of visual impairment, usually present at an early age. Both syndromic and non-syndromic congenital cataracts exhibit all modes of inheritance and may occur in association with various ocular or systemic abnormalities. Early diagnosis and treatment are crucial for the visual prognosis.

We applied next-generation sequencing (NGS) of clinical exome for identification of the disease-causing variants in a group of seven Bulgarian patients with syndromic and non-syndromic cataracts, accompanied by glaucoma with variable anterior segment defects and other ocular phenotypes.

Systematic filtering pipelines coupled with copy number variation analysis and segregation studies led to the identification of four pathogenic/likely pathogenic changes and two variants of uncertain significance (VUS), three of which were newly found. Candidate disease-causing variants in the CRYAA, CRYBB1, MYH9, RP2, CLNC1, and CACNA1S genes were found, which allowed the establishment of a precise genetic diagnosis of all of the studied pedigrees.

Our results confirm the usefulness of a targeted NGS approach based on clinical exome analysis as a comprehensive genetic diagnostic tool for syndromic and isolated cataracts with a significant impact on patient counseling.