A novel de novo <i>CAPN5</i> mutation in a patient with inflammatory vitreoretinopathy, hearing loss, and developmental delay

Abstract

Mutations that activate the protease calpain-5 (<i>CAPN5)</i> cause a nonsyndromic adult-onset autoinflammatory eye disease characterized by uveitis, altered synaptic signaling, retinal degeneration, neovascularization, and intraocular fibrosis. We describe a pediatric patient with severe inflammatory vitreoretinopathy accompanied by hearing loss and developmental delay associated with a novel, de novo <i>CAPN5</i> missense mutation (c.865C>T, p.Arg289Trp) that shows greater hyperactivation of the calpain protease, indicating a genotype-phenotype correlation that links mutation severity to proteolytic activity and the possibility of earlier onset syndromic disease with auditory and neurological abnormalities.