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| Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome |
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| Author(s): 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 |
| Source: NATURE Volume: 425 Issue: 6958 Pages: 628-633 Published: OCT 9 2003 |
| Times Cited: 236 References: 29 |
| 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(1-6), 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Katsanis, N (reprint author), Johns Hopkins Univ, Inst Med Genet, Baltimore, MD 21287 USA |
Addresses:
1. Johns Hopkins Univ, Inst Med Genet, Baltimore, MD 21287 USA
2. Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21287 USA
3. Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6 Canada
4. UCL, Inst Child Hlth, Mol Med Unit, London WC1N 1EH, England
5. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
6. Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA
7. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
8. Baylor Coll Med, Dept Med, Houston, TX 77030 USA
9. King Khalid Eye Specialist Hosp, Riyadh 11462, Saudi Arabia |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 729XU |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature02030 |
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