Expanding the phenotype ofCRYAAnucleotide variants to a complex presentation of anterior segment dysgenesis

Background Mutations inCRYAA, which encodes the alpha-crystallin protein, are associated with a spectrum of congenital cataract-microcornea syndromes. Results In this study, we performed clinical examination and subsequent genetic analysis in two unrelated sporadic cases of different geographical origins presenting with a complex phenotype of ocular malformation. Both cases manifested bilateral microphthalmia and severe anterior segment dysgenesis, primarily characterized by congenital aphakia, microcornea, and iris hypoplasia/aniridia. NGS-based analysis revealed two novel single nucleotide variants occurring de novo and affecting the translation termination codon of theCRYAAgene, c.520T > C and c.521A > C. Both variants are predicted to elongate the C-terminal protein domain by one-third of the original length. Conclusions Our report not only expands the mutational spectrum ofCRYAAbut also identifies the genetic cause of the unusual ocular phenotype described in this report.