Two Novel CAPN5 Variants Associated with Mild and Severe Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy Phenotypes

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.

Keywords:

• ADNIV
• Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy
• CAPN5
• CALPAIN-5
• UVEITIS

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding

This work is supported by the National Institute for Health Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the Wellcome Trust.

Additional information

Funding

This work is supported by the National Institute for Health Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the Wellcome Trust.