Abstract
Purpose: We report two new CAPN5 mutations associated with a phenotype of Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy. Methods: We performed next generation sequencing in two patients with ADNIV phenotype; the variants identified were explored further. Results: Patient 1 was heterozygous for CAPN5 c.799G>A, p.(Gly267Ser). Patient 2 was heterozygous for CAPN5 c.1126G>A, p.(Gly376Ser). Both amino acids are highly conserved across species. Patient 1 had a severe phenotype and his mutation lies within the protein's catalytic domain. Patient 2 had a mild phenotype and her mutation is the first ADNIV-causing mutation to be described in the regulatory domain of Calpain-5. Conclusions: Our findings potentially add two new ADNIV-causing CAPN5 mutations to the three previously described. We recommend CAPN5 genetic testing in all patients with a possible ADNIV phenotype, to develop our understanding of Calpain-5; a protein which could potentially provide therapeutically accessible targets for the treatment of many leading causes of blindness.