Catenin α 1 mutations cause familial exudative vitreoretinopathy by overactivating Norrin/β-catenin signaling.

ABSTRACT: Familial exudative vitreoretinopathy (FEVR) is a severe retinal vascular disease that causes blindness. FEVR has been linked to mutations in several genes associated with inactivation of the Norrin/β-catenin signaling pathway, but these account for only approximately 50% of cases. We report that mutations in α-catenin (CTNNA1) cause FEVR by overactivating the β-catenin pathway and disrupting cell adherens junctions. We identified 3 heterozygous mutations in CTNNA1 (p.F72S, p.R376Cfs*27, and p.P893L) by exome sequencing and further demonstrated that FEVR-associated mutations led to overactivation of Norrin/β-catenin signaling as a result of impaired protein interactions within the cadherin-catenin complex. The clinical features of FEVR were reproduced in mice lacking Ctnna1 in vascular endo

SUBMITTER: Zhu X 

PROVIDER: S-EPMC7954601 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature