Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.

Published

Journal Article

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized primarily by retinal dystrophy, obesity, polydactyly, renal malformations and learning disabilities. Although five BBS genes have been cloned, the molecular basis of this syndrome remains elusive. Here we show that BBS is probably caused by a defect at the basal body of ciliated cells. We have cloned a new BBS gene, BBS8, which encodes a protein with a prokaryotic domain, pilF, involved in pilus formation and twitching mobility. In one family, a homozygous null BBS8 mutation leads to BBS with randomization of left-right body axis symmetry, a known defect of the nodal cilium. We have also found that BBS8 localizes specifically to ciliated structures, such as the connecting cilium of the retina and columnar epithelial cells in the lung. In cells, BBS8 localizes to centrosomes and basal bodies and interacts with PCM1, a protein probably involved in ciliogenesis. Finally, we demonstrate that all available Caenorhabditis elegans BBS homologues are expressed exclusively in ciliated neurons, and contain regulatory elements for RFX, a transcription factor that modulates the expression of genes associated with ciliogenesis and intraflagellar transport.

Full Text

Duke Authors

Cited Authors

  • Ansley, SJ; Badano, JL; Blacque, OE; Hill, J; Hoskins, BE; Leitch, CC; Kim, JC; Ross, AJ; Eichers, ER; Teslovich, TM; Mah, AK; Johnsen, RC; Cavender, JC; Lewis, RA; Leroux, MR; Beales, PL; Katsanis, N

Published Date

  • October 1, 2003

Published In

Volume / Issue

  • 425 / 6958

Start / End Page

  • 628 - 633

PubMed ID

  • 14520415

Pubmed Central ID

  • 14520415

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature02030

Language

  • eng