The nonmotile ciliopathies.

Over the last 5 years, disorders of nonmotile cilia have come of age and their study has contributed immeasurably to our understand- ing of cell biology and human genetics. This review summarizes the main features of the ciliopathies, their underlying genetics, and the functions of the proteins involved. We describe some of the key findings in the field, including new animal models, the role of ciliopathy proteins in signaling pathways and development, and the unusual genetics of these diseases. We also discuss the therapeutic potential for these diseases and finally, discuss important future work that will extend our understanding of this fascinating organelle and its associated pathologies. Genet Med 2009:11(6):386-402. The ciliopathies form a class of genetic disease whose etiology lies with primary ciliary dysfunction. Although many of these syndromes have been recognized as isolated entities, it has only been in the last few years that this seemingly disparate collection of rare and clinically perplexing disorders has been classified. The term "nonmotile ciliopathy" refers to diseases that tend only to affect the function of nonmotile, primary cilia, and not the motile cilia, familiarly lining epithelia and powering sperm movement. Many disease gene products localize to the basal bodies and centrosomes too, but here we only refer to those conditions where the phenotype can be ascribed to aberrant cilia function or signaling. The list of bona fide ciliopathies continues to grow and at present includes Bardet-Biedl syndrome (BBS), nephronophthisis (NPHP), Senior-Loken syndrome (SNLS), Alstrom syndrome (ALMS), Meckel syndrome (MKS), Joubert syndrome (JBTS), Oral-facial-digital Type I (OFD 1), Jeune as- phyxiating thoracic dystrophy (JATD), Ellis van Creveld (EVC), and Leber congenital amaurosis (LCA). Polycystic kidney diseases (PKD) both the recessive and dominant forms should also techni- cally be regarded ciliopathies. In view of the existing and extensive literature on these disorders, they will not be discussed here and the reader is referred to relevant reviews.1,2