Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts.

Lens development is orchestrated by transcription factors. Disease-causing variants in transcription factors and their developmental target genes are associated with congenital cataracts and other eye anomalies. Using whole exome sequencing, we identified disease-causing variants in two large British families and one isolated case with autosomal dominant congenital cataract. Bioinformatics analysis confirmed these disease-causing mutations as rare or novel variants, with a moderate to damaging pathogenicity score, with testing for segregation within the families using direct Sanger sequencing. Family A had a missense variant (c.184 G>A; p.V62M) in PAX6 and affected individuals presented with nuclear cataract. Family B had a frameshift variant (c.470-477dup; p.A160R*) in PITX3 that was also associated with nuclear cataract. A recurrent missense variant in HSF4 (c.341 T>C; p.L114P) was associated with congenital cataract in a single isolated case. We have therefore identified novel variants in PAX6 and PITX3 that cause autosomal dominant congenital cataract. © 2021. Crown.

Citation

Vanita Berry, Alex Ionides, Nikolas Pontikos, Anthony T Moore, Roy A Quinlan, Michel Michaelides. Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts. Eye (London, England). 2022 Aug;36(8):1694-1701

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PMID: 34345029

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