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, DNAI1 and DNAH5, underlie PCD in nearly half of the patients with ODA defects, whereas RPGR, DNAH11 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 DNAI2 is currently being assessed. In all the other patients with ODA or other ultrastructural defects, the causative genes remain to be identified.
Escudier
Estelle
E
AP-HP, Service de Génétique et d'Embryologie médicales and Inserm U.933, Hôpital Armand-Trousseau, 26, avenue du Docteur Arnold-Netter, 75571 Paris Cedex 13, France. estelle.escudier@trs.aphp.fr
Duquesnoy
Philippe
P
Papon
Jean François
JF
Amselem
Serge
S
D056444:Axonemal Dyneins; D002923:Cilia / Q000235:genetics; D002925:Ciliary Motility Disorders / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004398:Dyneins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D009154:Mutation; D010641:Phenotype; D011379:Prognosis
D004247:DNA; D056444:Axonemal Dyneins; C465433:DNAH11 protein, human; C497507:DNAH5 protein, human; D004398:Dyneins