Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome (original) (raw)

• Letter
• Published: 21 September 2003
• Jose L. Badano1 na1,
• Oliver E. Blacque3 na1,
• Josephine Hill4,
• Bethan E. Hoskins1,4,
• Carmen C. Leitch1,
• Jun Chul Kim3,
• Alison J. Ross4,
• Erica R. Eichers5,
• Tanya M. Teslovich1,
• Allan K. Mah3,
• Robert C. Johnsen3,
• John C. Cavender7,
• Richard Alan Lewis5,6,
• Michel R. Leroux3,
• Philip L. Beales4 &
• …
• Nicholas Katsanis1,2

Nature volume 425, pages 628–633 (2003)Cite this article

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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 cloned1,2,3,4,5,6, 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.

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Acknowledgements

We thank all the BBS families for their willing and continued participation in our studies; J. Sowden, S. Darling and R. Graham for technical help; and J. Lupski, A. Chakravarti, J. Nathans, P. Scambler, A. McCallion and L. Kotch for their critical evaluation of this manuscript. We also thank J. Morton for clinical details and J. Goodship for discussions. This study was supported by grants from the National Institute of Child Health and Development, NIH and the March of Dimes (N.K.), the Research Department of the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia (J.C.C., R.A.L.), the Foundation Fighting Blindness, USA (R.A.L.), the Research to Prevent Blindness, New York (R.A.L.), NCIC, HSFBC&Y, CIHR and MSFHR (M.R.L.), NSERC (R.C.J.), Genome BC and Genome Canada (R.C.J., K.M.), the National Kidney Research Fund (B.E.H.), the Birth Defects Foundation (P.L.B.), and the Wellcome Trust (P.L.B.).

Authors' contributions The laboratories of M.R.L., P.L.B. and N.K. contributed equally to this work.

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Author notes

1. Stephen J. Ansley, Jose L. Badano and Oliver E. Blacque: These authors contributed equally to this work

Authors and Affiliations

1. Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, 21287, USA
   Stephen J. Ansley, Jose L. Badano, Bethan E. Hoskins, Carmen C. Leitch, Tanya M. Teslovich & Nicholas Katsanis
2. Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, 21287, USA
   Nicholas Katsanis
3. Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada
   Oliver E. Blacque, Jun Chul Kim, Allan K. Mah, Robert C. Johnsen & Michel R. Leroux
4. Molecular Medicine Unit, Institute of Child Health, University College London, WC1N 1EH, London, UK
   Josephine Hill, Bethan E. Hoskins, Alison J. Ross & Philip L. Beales
5. Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA
   Erica R. Eichers & Richard Alan Lewis
6. Departments of Ophthalmology, Pediatrics, and Medicine, Baylor College of Medicine, Houston, Texas, 77030, USA
   Richard Alan Lewis
7. King Khaled Eye Hospital, Riyadh, 11462, Saudi Arabia
   John C. Cavender

Authors

1. Stephen J. Ansley
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2. Jose L. Badano
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3. Oliver E. Blacque
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4. Josephine Hill
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5. Bethan E. Hoskins
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6. Carmen C. Leitch
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9. Erica R. Eichers
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10. Tanya M. Teslovich
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11. Allan K. Mah
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Correspondence toNicholas Katsanis.

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Ansley, S., Badano, J., Blacque, O. et al. Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome.Nature 425, 628–633 (2003). https://doi.org/10.1038/nature02030

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• Received: 24 June 2003
• Accepted: 08 September 2003
• Published: 21 September 2003
• Issue Date: 09 October 2003
• DOI: https://doi.org/10.1038/nature02030

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