Figure 3.

WNT pathway mutations underlie vitreoretinopathies that have phenotypic overlap with pathologies seen in the DC spectrum diseases. Exudative retinopathies are a component of two telomere disorders (Coats plus and Revesz syndrome), and their retinal appearance is similar to that observed in familial exudative vitreoretinopathy (FEVR) and Coats’ disease. FEVR is caused by mutations in genes encoding a WNT signaling pathway (LRP5, FRZD4, TSPAN12, RCBTB1, and CTNNB1 (β-catenin)) utilized by the NORRIN protein, and Coats’ diseases is associated with mutations in NORRIN and RCBTB1. It is therefore possible that the retinopathies in telomere disorders are caused by inhibition of WNT pathway activity induced by telomere dysfunction.