Orphanet Journal of Rare Diseases (Aug 2020)

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

  • Andrey V. Marakhonov,
  • Anna A. Voskresenskaya,
  • Maria Jose Ballesta,
  • Fedor A. Konovalov,
  • Tatyana A. Vasilyeva,
  • Fiona Blanco-Kelly,
  • Nadezhda A. Pozdeyeva,
  • Vitaly V. Kadyshev,
  • Vanesa López-González,
  • Encarna Guillen,
  • Carmen Ayuso,
  • Rena A. Zinchenko,
  • Marta Corton

Journal volume & issue
Vol. 15, no. 1
pp. 1 – 10


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Abstract 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.