Ciliary defects and genetics of primary ciliary dyskinesia

Cilia are evolutionarily conserved structures that play key roles in diverse cell types. Motile cilia are involved in the most prominent ciliopathy called primary ciliary dyskinesia (PCD) that combines respiratory symptoms, male infertility, and, in nearly 50% cases, situs inversus. The diagnosis of PCD relies on the identification of ciliary abnormalities that mainly concern outer and/or inner dynein arms (ODA, IDA). PCD is a genetic condition, usually inherited as an autosomal recessive trait. To date, six genes have been clearly implicated in PCD. Two "major" genes, DNA/1 and DNAH5, underlie PCD in nearly hall of the patients with ODA defects, whereas RPGR, DNAH1 1 and TXNDC3 are implicated in rare families with specific phenotypes (retinitis pigmentosa, abnormal beating of structurally normal cilia, and situs ambiguous, respectively). The relative contribution of DNA12 is currently being assessed. In all the other patients with ODA or other ultrastructural defects, the causative genes remain to be identified. (C) 2009 Elsevier Ltd. All rights reserved.