Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy

Nature Genetics volume 42, pages 840–850 (2010)Cite this article

Subjects

Abstract

Nephronophthisis-related ciliopathies (NPHP-RC) are recessive disorders that feature dysplasia or degeneration occurring preferentially in the kidney, retina and cerebellum. Here we combined homozygosity mapping with candidate gene analysis by performing 'ciliopathy candidate exome capture' followed by massively parallel sequencing. We identified 12 different truncating mutations of SDCCAG8 (serologically defined colon cancer antigen 8, also known as CCCAP) in 10 families affected by NPHP-RC. We show that SDCCAG8 is localized at both centrioles and interacts directly with OFD1 (oral-facial-digital syndrome 1), which is associated with NPHP-RC. Depletion of sdccag8 causes kidney cysts and a body axis defect in zebrafish and induces cell polarity defects in three-dimensional renal cell cultures. This work identifies loss of SDCCAG8 function as a cause of a retinal-renal ciliopathy and validates exome capture analysis for broadly heterogeneous single-gene disorders.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Homozygosity mapping, exon capture and massively parallel sequencing identifies SDCCAG8 mutations as causing nephronophthisis with retinal degeneration.
Figure 2: Indirect immunofluorescence detects SDCCAG8 at centrosomes together with other proteins disrupted in NPHP-RC.
Figure 3: SDCCAG8 interacts with OFD1.
Figure 4: SDCCAG8 is located in mouse photoreceptor basal bodies and the connecting cilia transition zone.
Figure 5: Knockdown of zebrafish sdccag8 results in multiple developmental defects.
Figure 6: siRNA knockdown of Sdccag8 perturbs lumen formation of renal epithelial cells in 3D spheroid culture.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Hildebrandt, F. et al. A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1. Nat. Genet. 17, 149–153 (1997).

    Article  CAS  PubMed  Google Scholar 

  2. Otto, E.A. et al. Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat. Genet. 34, 413–420 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Olbrich, H. et al. Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis. Nat. Genet. 34, 455–459 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. Otto, E. et al. A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution. Am. J. Hum. Genet. 71, 1167–1171 (2002).

    Article  Google Scholar 

  5. Mollet, G. et al. The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin. Nat. Genet. 32, 300–305 (2002).

    Article  CAS  PubMed  Google Scholar 

  6. Otto, E. et al. Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin. Nat. Genet. 37, 282–288 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Sayer, J.A. et al. The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat. Genet. 38, 674–681 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Valente, E.M. et al. Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome. Nat. Genet. 38, 623–625 (2006).

    Article  CAS  PubMed  Google Scholar 

  9. Attanasio, M. et al. Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis. Nat. Genet. 39, 1018–1024 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. Delous, M. et al. The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat. Genet. 39, 875–881 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Otto, E.A. et al. NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis. J. Am. Soc. Nephrol. 19, 587–592 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hildebrandt, F. & Zhou, W. Nephronophthisis-associated ciliopathies. J. Am. Soc. Nephrol. 18, 1855–1871 (2007).

    Article  CAS  PubMed  Google Scholar 

  13. Hildebrandt, F. et al. A systematic approach to mapping recessive disease genes in individuals from outbred populations. PLoS Genet. 5, 31000353 (2009).

    Article  Google Scholar 

  14. Ng, S.B. et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461, 272–276 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liu, Q. et al. The proteome of the mouse photoreceptor sensory cilium complex. Mol. Cell. Proteomics 6, 1299–1317 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Gherman, A., Davis, E.E. & Katsanis, N. The ciliary proteome database: an integrated community resource for the genetic and functional dissection of cilia. Nat. Genet. 38, 961–962 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Zhang, X.H., Kangsamaksin, T., Chao, M.S., Banerjee, J.K. & Chasin, L.A. Exon inclusion is dependent on predictable exonic splicing enhancers. Mol. Cell. Biol. 25, 7323–7332 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Baker, K. & Beales, P.L. Making sense of cilia in disease: the human ciliopathies. Am. J. Med. Genet. C. Semin. Med. Genet. 151C, 281–295 (2009).

    Article  CAS  PubMed  Google Scholar 

  19. Beales, P.L., Elcioglu, N., Woolf, A.S., Parker, D. & Flinter, F.A. New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J. Med. Genet. 36, 437–446 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Kenedy, A.A., Cohen, K.J., Loveys, D.A., Kato, G.J. & Dang, C.V. Identification and characterization of the novel centrosome-associated protein CCCAP. Gene 303, 35–46 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Simms, R.J., Eley, L. & Sayer, J.A. Nephronophthisis. Eur. J. Hum. Genet. 17, 406–416 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Graser, S. et al. Cep164, a novel centriole appendage protein required for primary cilium formation. J. Cell Biol. 179, 321–330 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Andersen, J.S. et al. Proteomic characterization of the human centrosome by protein correlation profiling. Nature 426, 570–574 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. Watnick, T. & Germino, G. From cilia to cyst. Nat. Genet. 34, 355–356 (2003).

    Article  CAS  PubMed  Google Scholar 

  25. Delous, M. et al. Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6. Hum. Mol. Genet. 18, 4711–4723 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Coene, K.L. et al. OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin. Am. J. Hum. Genet. 85, 465–481 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Thauvin-Robinet, C. et al. Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study. J. Med. Genet. 43, 54–61 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Budny, B. et al. A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. Hum. Genet. 120, 171–178 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Rakkolainen, A., Ala-Mello, S., Kristo, P., Orpana, A. & Jarvela, I. Four novel mutations in the OFD1 (Cxorf5) gene in Finnish patients with oral-facial-digital syndrome 1. J. Med. Genet. 39, 292–296 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ferrante, M.I. et al. Identification of the gene for oral-facial-digital type I syndrome. Am. J. Hum. Genet. 68, 569–576 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Schluter, M.A. & Margolis, B. Apical lumen formation in renal epithelia. J. Am. Soc. Nephrol. 20, 1444–1452 (2009).

    Article  PubMed  Google Scholar 

  32. Elia, N. & Lippincott-Schwartz, J. Culturing MDCK cells in three dimensions for analyzing intracellular dynamics. Curr. Protoc. Cell Biol. Chapter 4 Unit 4 22 (2009).

  33. Kim, E. & Walz, G. Sensitive cilia set up the kidney. Nat. Med. 13, 1409–1411 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Moyer, J.H. et al. Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice. Science 264, 1329–1333 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Torres, V.E. Role of vasopressin antagonists. Clin. J. Am. Soc. Nephrol. 3, 1212–1218 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Gattone, V.H. II, Wang, X., Harris, P.C. & Torres, V.E. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat. Med. 9, 1323–1326 (2003).

    Article  CAS  PubMed  Google Scholar 

  37. Patel, V., Chowdhury, R. & Igarashi, P. Advances in the pathogenesis and treatment of polycystic kidney disease. Curr. Opin. Nephrol. Hypertens. 18, 99–106 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kruglyak, L., Daly, M.J., Reeve-Daly, M.P. & Lander, E.S. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am. J. Hum. Genet. 58, 1347–1363 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Strauch, K. et al. Parametric and nonparametric multipoint linkage analysis with imprinting and two-locus-trait models: application to mite sensitization. Am. J. Hum. Genet. 66, 1945–1957 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gudbjartsson, D.F., Jonasson, K., Frigge, M.L. & Kong, A. Allegro, a new computer program for multipoint linkage analysis. Nat. Genet. 25, 12–13 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Khanna, H. et al. A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nat. Genet. 41, 739–745 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Matsuda, M. et al. The administration of retinoic acid down-regulates cAMP-responsive element modulator (CREM) mRNA in vitamin A-deficient testes. Biosci. Biotechnol. Biochem. 69, 261–266 (2005).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank families and study subjects for their contributions and E. Nigg for the OFD1 antibody. This research was supported by grants from the National Institutes of Health to F.H. (DK1069274, DK1068306, DK064614), to H.K. (EY007961), to D.S.W. (EY13408), to N.K. (HD042601, DK075972, DK072301) and to E.A.P. (EY12910); by grants from the Netherlands Organization for Scientific Research to K.L.M.C. (NWO Toptalent-021.001.014), to R.R. (NWO Vidi-91786396) and to R.H.G. (NWO Vidi-917.66.354); by the WellChild and Wellcome Trust to E.R.M.; by the Avenir-INSERM program, the Agence Nationale pour la Recherche, the Union Nationale pour les Aveugles et Déficients Visuels, RETINA France, Programme Hospitalier de Recherche National 2007 and the Association Bardet-Biedl, France to H.D., C.S. and E.A.P. by the Foundation Fighting Blindness, the Research to Prevent Blindness, the F.M. Kirby Foundation and the Rosanne Silbermann Foundation to E.A.P.; by the Midwest Eye Banks and Transplantation Center and Rare Disease Initiative, University of Michigan to H.K.; by Instituto Gulbenkian de Ciência and EMBO to M.B.D.; by the Deutsche Nierenstiftung, PKD Foundation and DFG (BE 3910/5-1 and SFB/TRR57) to C.B.; by CIHR, FFB-Canada, FRSQ and Reseau Vision to R.K.K.; by the “Else Kröner-Fresenius-Stiftung” (P66/09//A75/09) to H.P.H.N.; and by EU FP7 Consortium “SYSCILIA” to R.H.G., R.R. and N.K. F.H. is an Investigator of the Howard Hughes Medical Institute, a Doris Duke Distinguished Clinical Scientist and a Frederick G. L. Huetwell Professor. D.S.W. is a Jules and Doris Stein RPB professor. N.K. is a George R. Brumley Professor. S.S. is a laureate of the Equipe FRM (Dequation (20071210558)) and the Agence National de la Recherche (R07089KS). We thank the physicians who contributed to this study; A. Toutain, M.-C. Gubler, R. Salomon, M.-A. Macher and M. Fischbach for clinical data; S.J. Allen, A. Saveliev and Y. Liu for technical assistance; K. Tory and C. Becker for linkage analysis and exon sequencing; S. Shi and R. Insolera for shRNA clones; C. Janke for the GT335 antibody; J. Salisbury for the centrin-2 antibody; E. Nigg for the CEP164 antibody; and B. Chang for the CEP290 antibody.

Author information

Author notes

  1. Edgar A Otto and Toby W Hurd: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA

    Edgar A Otto, Toby W Hurd, Rannar Airik, Moumita Chaki, Weibin Zhou, Amiya K Ghosh, Heather M McLaughlin, Susanne Held, Jennifer M Kasanuki, Gokul Ramaswami, James MacDonald & Friedhelm Hildebrandt

  2. Laboratoire de Génétique Médicale EA3949, Equipe AVENIR-Inserm, Faculté de Médecine, Université de Strasbourg, Strasbourg, France

    Corinne Stoetzel & Helene Dollfus

  3. Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA

    Suresh B Patil, Carlos A Murga-Zamalloa & Hemant Khanna

  4. HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA

    Shawn Levy

  5. Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Jeroen van Reeuwijk, Stef J F Letteboer, Karlien L M Coene, Alejandro Estrada-Cuzcano, Rob W J Collin & Ronald Roepman

  6. Department of Cell Regulation, Genentech Inc., South San Francisco, California, USA

    Liyun Sang & Peter K Jackson

  7. Department of Medical Oncology, University Medical Center, Utrecht, The Netherlands

    Rachel H Giles

  8. F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

    Qin Liu & Eric A Pierce

  9. Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA

    Heather M McLaughlin & Friedhelm Hildebrandt

  10. McGill Ocular Genetics Laboratory, Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada

    Jinny Conte, Irma Lopez & Robert K Koenekoop

  11. University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA

    Joseph Washburn

  12. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA

    Jinghua Hu

  13. Department of Cell and Developmental Biology, University of Michigan, Michigan, USA

    Yukiko Yamashita

  14. Department of Medical and Molecular Genetics, School of Clinical and Experimental Medicine and Centre for Rare Diseases and Personalised Medicine, University of Birmingham, Institute of Biomedical Research, Edgbaston, Birmingham, UK

    Eamonn R Maher

  15. UAB Center for Clinical and Translational Science, University of Alabama at Birmingham, Birmingham, Alabama, USA

    Lisa M Guay-Woodford

  16. Department of Nephrology and General Medicine, University Medical Center, Albert-Ludwigs-University, Freiburg, Germany

    Hartmut P H Neumann

  17. Department of Nephrology, III. Medical Clinic, University Hospital, Frankfurt, Germany

    Nicholas Obermüller

  18. Department of Human Genetics, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany

    Carsten Bergmann

  19. Center for Human Disease Modeling, Duke University Medical Center, Durham, North Carolina, USA

    Xiaoshu Bei & Nicholas Katsanis

  20. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA

    Xiaoshu Bei & Nicholas Katsanis

  21. Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA

    Xiaoshu Bei & Nicholas Katsanis

  22. Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA

    Richard A Lewis

  23. Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, California, USA

    Vanda Lopes & David S Williams

  24. Department of Biological Chemistry and DNA Sequencing Core, University of Michigan, Ann Arbor, Michigan, USA

    Robert H Lyons

  25. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Chi V Dang

  26. Instituto Gulbenkian de Ciência, Oeiras, Portugal

    Daniela A Brito & Mónica Bettencourt Dias

  27. Roche NimbleGen, Inc., Madison, Wisconsin, USA

    Xinmin Zhang

  28. Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA

    James D Cavalcoli

  29. Cologne Center for Genomics, University of Cologne, Cologne, Germany

    Gudrun Nürnberg & Peter Nürnberg

  30. Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany

    Gudrun Nürnberg & Peter Nürnberg

  31. Cologne Excellence Cluster on Cellular Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany

    Gudrun Nürnberg & Peter Nürnberg

  32. Department of Genetics, Hôpital Necker-Enfants Malades, Assistance Publique–Hôpitaux de Paris, Paris, France

    Corinne Antignac & Sophie Saunier

  33. INSERM U-983, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France

    Corinne Antignac

  34. Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Ronald Roepman

  35. Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Helene Dollfus

  36. Howard Hughes Medical Institute, Chevy Chase, Maryland, USA

    Friedhelm Hildebrandt

Authors
  1. Edgar A Otto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toby W Hurd
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rannar Airik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Moumita Chaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Weibin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Corinne Stoetzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Suresh B Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shawn Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Amiya K Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carlos A Murga-Zamalloa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jeroen van Reeuwijk
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Stef J F Letteboer
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Liyun Sang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Rachel H Giles
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Qin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Karlien L M Coene
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Alejandro Estrada-Cuzcano
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Rob W J Collin
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Heather M McLaughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Susanne Held
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Jennifer M Kasanuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Gokul Ramaswami
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Jinny Conte
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Irma Lopez
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Joseph Washburn
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. James MacDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Jinghua Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Yukiko Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Eamonn R Maher
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Lisa M Guay-Woodford
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Hartmut P H Neumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Nicholas Obermüller
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. Robert K Koenekoop
    View author publications

    You can also search for this author in PubMed Google Scholar

  34. Carsten Bergmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  35. Xiaoshu Bei
    View author publications

    You can also search for this author in PubMed Google Scholar

  36. Richard A Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  37. Nicholas Katsanis
    View author publications

    You can also search for this author in PubMed Google Scholar

  38. Vanda Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  39. David S Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  40. Robert H Lyons
    View author publications

    You can also search for this author in PubMed Google Scholar

  41. Chi V Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

  42. Daniela A Brito
    View author publications

    You can also search for this author in PubMed Google Scholar

  43. Mónica Bettencourt Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

  44. Xinmin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  45. James D Cavalcoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  46. Gudrun Nürnberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  47. Peter Nürnberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  48. Eric A Pierce
    View author publications

    You can also search for this author in PubMed Google Scholar

  49. Peter K Jackson
    View author publications

    You can also search for this author in PubMed Google Scholar

  50. Corinne Antignac
    View author publications

    You can also search for this author in PubMed Google Scholar

  51. Sophie Saunier
    View author publications

    You can also search for this author in PubMed Google Scholar

  52. Ronald Roepman
    View author publications

    You can also search for this author in PubMed Google Scholar

  53. Helene Dollfus
    View author publications

    You can also search for this author in PubMed Google Scholar

  54. Hemant Khanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  55. Friedhelm Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

E.A.O., H.M.M., S.H., J.M.K. and G.R. generated total genome linkage, exon capture and gene identification data. T.W.H. generated antibody characterization, immunoprecipitation and cell cycle expression data. R.A., M.C., H.K., A.K.G., S.B.P., C.A.M.-Z., J.H., Y.Y. and C.V.D. performed immunofluorescence and subcellular localization studies by confocal microscopy. W.Z. performed zebrafish experiments. J.v.R., S.J.F.L. and R.R. contributed the OFD1 work. L.S., R.H.G. and P.K.J. generated spheroid assay and protein expression data. Q.L. and E.A.P. performed retinal electroporation studies. C.A., S.S., E.R.M., L.M.G.-W., H.P.H.N., N.O. and C.B. recruited patients and gathered detailed clinical information for the study. N.K., X.B., R.A.L., R.K.K., J.C., I.L., K.L.M.C., A.E.-C. and R.W.J.C. performed mutation analysis. D.A.B., M.B.D., Q.L., E.A.P., V.L. and D.S.W. performed high-resolution confocal microscopy and EM studies. S.L., R.H.L. and X.Z. performed large-scale sequencing or exon capture. G.N., P.N., F.H., J.D.C., J.W. and J.M. did linkage calculations. H.D. and C.S. independently mapped and identified SDCCAG8 in families FII.22 and FI.2. F.H. conceived and directed the project and wrote the paper with contributions from R.R., M.B.D. and H.D.

Corresponding author

Correspondence to Friedhelm Hildebrandt.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–10 and Supplementary Tables 1–3. (PDF 2299 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Otto, E., Hurd, T., Airik, R. et al. Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nat Genet 42, 840–850 (2010). https://doi.org/10.1038/ng.662

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.662

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing