Molecular and genetic mechanism of non-syndromic congenital cataracts. Mutation screening in Spanish families

Our purpose was to identify mutations responsible for non-syndromic congenital cataracts through the implementation of next-generation sequencing (NGS) in our center. A sample of peripheral blood was obtained from probands and willing family members and genomic DNA was extracted from leukocytes. DNA was analyzed implementing a panel (OFTv2.1) including 39 known congenital cataracts disease genes. 62 probands from 51 families were recruited. Pathogenic or likely pathogenic variants were identified in 32 patients and 25 families; in 16 families (64%) these were de novo mutations. The mutation detection rate was 49%. Almost all reported mutations were autosomal dominant. Mutations in crystallin genes were found in 30% of the probands. Mutations in membrane proteins were detected in seven families (two in GJA3 and five in GJA8). Mutations in LIM2 and MIP were each found in three families. Other mutations detected affected EPHA2, PAX6, HSF4 and PITX3. Variants classified as of unknown significance were found in 5 families (9.8%), affecting CRYBB3, LIM2, EPHA2, ABCB6 and TDRD7. Mutations lead to different cataract phenotypes within the same familyThis research was funded by ONCE grant number 2020/0197782 and by FIS grant number PI18-1234-ISCII