The Role of Connexins in Human Disease

In Brief Connexins are the building blocks of gap junctions. In forming a gap junction, six connexins oligomerize to form a hexameric torus called a connexon. The number of gap junctions in a cell ranges from a few to over 105 and imparts to interconnected cells a uniform phenotype. The crucial role that gap junctions play in normal physiology is reflected by the diverse spectrum of human diseases in which allele variants of different gap junction genes are implicated. In particular, mutations in GJB2 are a major cause of autosomal recessive non-syndromic deafness. This discovery has impacted medical practice and makes it incumbent on clinicians to familiarize themselves with the genetic advances that are rapidly occurring in our field. Connexins are proteins that form the building blocks for intercellular channels. These channels play many roles in normal physiology. Importantly, mutations in genes encoding connexins (in particular the GJB2 gene, which encodes connexin 26) are a major cause of nonsyndromic deafness. This article reviews the role of connexins in human disease, with a particular focus on deafness.