1. ¹King's College London, The Guy's, King's College and St Thomas' School of Medicine, Genetic Skin Disease Group, Division of Genetics and Molecular Medicine, St John's Institute of Dermatology, London, UK
2. ²Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Correspondence: Dr John A. McGrath, St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK. E-mail: john.mcgrath@kcl.ac.uk

Received 13 September 2006; Revised 6 November 2006; Accepted 29 November 2006.

Abstract

Tight junctions, gap junctions, adherens junctions, and desmosomes represent intricate structural intercellular channels and bridges that are present in several tissues, including epidermis. Clues to the important function of these units in epithelial cell biology have been gleaned from a variety of studies including naturally occurring and engineered mutations, animal models and other in vitro experiments. In this review, we focus on mutations that have been detected in human diseases. These observations provide intriguing insight into the biological complexities of cell–cell contact and intercellular communication as well as demonstrating the spectrum of inherited human diseases that are associated with mutations in genes encoding the component proteins. Over the last decade or so, human gene mutations have been reported in four tight junction proteins (claudin 1, 14, 16, and zona occludens 2), nine gap junction proteins (connexin 26, 30, 30.3, 31, 32, 40, 43, 46, and 50), one adherens junction protein (P-cadherin) and eight components of desmosomes (plakophilin (PKP) 1 and 2, desmoplakin, plakoglobin – which is also present in adherens junctions, desmoglein (DSG) 1, 2, 4, and corneodesmosin). These discoveries have often highlighted novel or unusual phenotypes, including abnormal skin barrier function, alterations in epidermal differentiation, and developmental anomalies of various ectodermal appendages, especially hair, as well as a range of extracutaneous pathologies. However, this review focuses mainly on inherited disorders of junctions that have an abnormal skin phenotype.