Cellular mechanisms of connexin-based inherited diseases

Abstract

The 21-member connexin gene family exhibits distinct tissue expression patterns that can cause a diverse array of over 30 inherited connexin-linked diseases ranging from deafness to skin defects and blindness. Intriguingly, germline mutations can cause disease in one tissue while other tissues that abundantly express the mutant connexin remain disease free, highlighting the importance of the cellular context of mutant expression. Modeling connexin pathologies in genetically modified mice and tissue-relevant cells has informed extensively on no less than a dozen gain- and loss-of-function mechanisms that underpin disease. This review focuses on how a deeper molecular understanding of the over 930 mutations in 11 connexin-encoding genes is foundational for creating a framework for therapeutic interventions.

Keywords: connexins; gap junctions; inherited disease; mutations.