Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis (original) (raw)

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References

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Acknowledgements

We thank the LCA families for their participation; H. Brunner, C. Johnson, N. Knoers and H. Kremer for discussions; C.J. Gloeckner for the TAPe constructs; T. Goldmann, E. Sehn, J. Hehir-Kwa, I. Janssen, K. Voesenek, A. Schumacher and S. Schöffmann for technical assistance; K. Klima, R. Pigeon and C. Robert for organizing the clinical data from affected individuals; S. Yzer, L.I. van den Born, S. Kohl, B. Wissinger, E. de Baere, B.P. Leroy, W. Bergen, K. Rohrschneider and C.B. Hoyng for sharing patient samples; and the Marshfield Mammalian Genotyping Service for carrying out genotyping in the Pakistani families. This research was supported by grants from The Netherlands Organisation for Scientific Research (916.56.160 to A.I.d.H.); the Foundation Fighting Blindness USA (BR-GE-0606-0349-RAD to A.I.d.H.); the Dutch Kidney Foundation (C04.2112 to R.R.); Landelijke Stichting voor Blinden en Slechtzienden (to A.I.d.H. and F.P.M.C.); Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (to A.I.d.H., R.R. and F.P.M.C); Rotterdamse Vereniging Blindenbelangen (to R.R. and F.P.M.C.); Stichting Blindenhulp (to R.R. and F.P.M.C.); Stichting OOG (to R.R. and F.P.M.C.); the British Retinitis Pigmentosa Society (GR552 to R.R.); the European Union 6th Framework RETNET (MRTNCT-2003-504003 to F.P.M.C. and M.U.), EVI-GENORET (LSHG-CT-2005 512036 to M.U., F.P.M.C. and R.R.) and INTERACTION PROTEOME (LSHG-CT-2003-505520 to M.U.); the Wellcome Trust (061682 and 073477 to C.F.I. and M.D.M., and 068579 to M.E.C.); Yorkshire Eye Research (006 to C.F.I.); the Foundation Fighting Blindness Canada (to R.K.K. and F.P.M.C.); the Fonds de la Recherche en Santé Québec; TD Financial Group (to R.K.K.); Foundation of Retinal Research; The Grousbeck Foundation; The Edel and Krieble Funds; the Ort Family Foundation (to I.H.M., S.D. and R.K.K.); Pro Retina Germany (to M.U. and R.R.); Deutsche Forschungsgemeinschaft (Wo 548-6 to U.W.), FAUN-Stiftung (to U.W.) and Forschung contra Blindheit (to U.W.).

Author information

Author notes

1. Anneke I den Hollander, Robert K Koenekoop, Moin D Mohamed, Heleen H Arts, Frans P M Cremers, Chris F Inglehearn and Ronald Roepman: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
   Anneke I den Hollander, Heleen H Arts, Ilse Gosens, Ferry F J Kersten, Erwin van Wijk, Joris A Veltman, Marijke N Zonneveld, Sylvia E C van Beersum, Frans P M Cremers & Ronald Roepman
2. McGill Ocular Genetics Center, McGill University Health Center, Montreal, Canada
   Robert K Koenekoop & Irma Lopez
3. Section of Ophthalmology and Neurosciences, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK
   Moin D Mohamed, Katherine V Towns, Martin McKibbin, Lenka Ivings, Grange A Williams, Kelly Springell & Chris F Inglehearn
4. Department of Ophthalmology, St Thomas' Hospital, London, UK
   Moin D Mohamed & Sharola Dharmaraj
5. Institute of Human Genetics, GSF National Research Center for Environment and Health, Munich-Neuherberg, Germany
   Karsten Boldt, Monika Beer, Tim M Strom & Marius Ueffing
6. Institute of Human Genetics, Technical University Munich, Munich, Germany
   Karsten Boldt, Monika Beer & Tim M Strom
7. Institut für Zoologie, Johannes Gutenberg University, Mainz, Germany
   Tina Sedmak, Kerstin Nagel-Wolfrum & Uwe Wolfrum
8. Eye Department, Chancellor Wing, St James's University Hospital, Leeds, UK
   Martin McKibbin
9. Eye and Nutrition Research Group, FLAVIC, National Institute for Research on Agronomy, Dijon, France
   Lenka Ivings
10. Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK
    C Geoff Woods
11. Gene Tech Lab 146/1, Shadman Jail Road, Lahore, Pakistan
    Hussain Jafri
12. Department of Obstetrics and Gynaecology, King Edward Medical University, Lahore, Pakistan
    Yasmin Rashid
13. Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands
    Bert van der Zwaag
14. Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA
    Irene H Maumenee
15. Division of Molecular and Cellular Neuroscience, Institute of Ophthalmology, University College London, London, UK
    Michael E Cheetham

Authors

1. Anneke I den Hollander
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2. Robert K Koenekoop
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3. Moin D Mohamed
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4. Heleen H Arts
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5. Karsten Boldt
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6. Katherine V Towns
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7. Tina Sedmak
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8. Monika Beer
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9. Kerstin Nagel-Wolfrum
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10. Martin McKibbin
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11. Sharola Dharmaraj
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12. Irma Lopez
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13. Lenka Ivings
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14. Grange A Williams
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15. Kelly Springell
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16. C Geoff Woods
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17. Hussain Jafri
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18. Yasmin Rashid
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19. Tim M Strom
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20. Bert van der Zwaag
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21. Ilse Gosens
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22. Ferry F J Kersten
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23. Erwin van Wijk
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24. Joris A Veltman
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25. Marijke N Zonneveld
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26. Sylvia E C van Beersum
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27. Irene H Maumenee
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28. Uwe Wolfrum
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29. Michael E Cheetham
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30. Marius Ueffing
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31. Frans P M Cremers
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32. Chris F Inglehearn
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33. Ronald Roepman
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Corresponding author

Correspondence toAnneke I den Hollander.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Sequences of LCA5 mutations identified in LCA families. (PDF 26 kb)

Supplementary Fig. 2

Evolutionary conservation of lebercilin and C21ORF13 proteins. (PDF 21 kb)

Supplementary Fig. 3

Expression of the LCA5 gene in human tissues and mammalian cell lines, and detection of lebercilin in mouse tissues. (PDF 467 kb)

Supplementary Fig. 4

Expression of the recombinant lebercilin proteins in ARPE-19 and COS-1 cells. (PDF 328 kb)

Supplementary Fig. 5

Expression of the TAPe constructs and immunoprecipitation of lebercilin. (PDF 422 kb)

Supplementary Table 1

Refinement of the LCA5 interval in three Pakistani LCA families. (PDF 49 kb)

Supplementary Table 2

Homozygous chromosomal regions in patients 27240 and 28609. (PDF 46 kb)

Supplementary Table 3

Protein/peptide summaries of LC-MSMS analysis of tandem affinity-purified lebercilin protein complexes. (PDF 489 kb)

Supplementary Table 4

Primer sequences for amplification of the exons and splice junctions of the LCA5 gene. (PDF 48 kb)

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den Hollander, A., Koenekoop, R., Mohamed, M. et al. Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis.Nat Genet 39, 889–895 (2007). https://doi.org/10.1038/ng2066

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• Received: 31 January 2007
• Accepted: 10 May 2007
• Published: 03 June 2007
• Issue Date: July 2007
• DOI: https://doi.org/10.1038/ng2066