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

Nature. 2003 Oct 9;425(6958):628-33. doi: 10.1038/nature02030. Epub 2003 Sep 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Bardet-Biedl Syndrome / genetics*
  • Bardet-Biedl Syndrome / metabolism
  • Bardet-Biedl Syndrome / pathology*
  • Base Sequence
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Cell Line
  • Centrosome / metabolism
  • Centrosome / pathology
  • Cilia / metabolism
  • Cilia / pathology*
  • Female
  • Gene Deletion
  • Gene Expression Profiling
  • Homozygote
  • Humans
  • Lod Score
  • Male
  • Molecular Sequence Data
  • Mutation / genetics
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / pathology
  • Pedigree
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Proteins
  • RNA, Messenger
  • TTC8 protein, human

Associated data

  • GENBANK/AY366523
  • GENBANK/AY366524