Expanding the phenotype of CRYAA nucleotide variants to a complex presentation of anterior segment dysgenesis
Andrey V Marakhonov1, Anna A Voskresenskaya2, Maria Jose Ballesta3,4
1Research Centre for Medical Genetics, Moskvorechie Str., 1, Moscow, Russian Federation. marakhonov@generesearch.ru.
Background:
Mutations in CRYAA, which encodes the α-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 the CRYAA gene, 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 of CRYAA but also identifies the genetic cause of the unusual ocular phenotype described in this report.
