Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy (original) (raw)

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
   You can also search for this author inPubMed Google Scholar
2. Toby W Hurd
   You can also search for this author inPubMed Google Scholar
3. Rannar Airik
   You can also search for this author inPubMed Google Scholar
4. Moumita Chaki
   You can also search for this author inPubMed Google Scholar
5. Weibin Zhou
   You can also search for this author inPubMed Google Scholar
6. Corinne Stoetzel
   You can also search for this author inPubMed Google Scholar
7. Suresh B Patil
   You can also search for this author inPubMed Google Scholar
8. Shawn Levy
   You can also search for this author inPubMed Google Scholar
9. Amiya K Ghosh
   You can also search for this author inPubMed Google Scholar
10. Carlos A Murga-Zamalloa
    You can also search for this author inPubMed Google Scholar
11. Jeroen van Reeuwijk
    You can also search for this author inPubMed Google Scholar
12. Stef J F Letteboer
    You can also search for this author inPubMed Google Scholar
13. Liyun Sang
    You can also search for this author inPubMed Google Scholar
14. Rachel H Giles
    You can also search for this author inPubMed Google Scholar
15. Qin Liu
    You can also search for this author inPubMed Google Scholar
16. Karlien L M Coene
    You can also search for this author inPubMed Google Scholar
17. Alejandro Estrada-Cuzcano
    You can also search for this author inPubMed Google Scholar
18. Rob W J Collin
    You can also search for this author inPubMed Google Scholar
19. Heather M McLaughlin
    You can also search for this author inPubMed Google Scholar
20. Susanne Held
    You can also search for this author inPubMed Google Scholar
21. Jennifer M Kasanuki
    You can also search for this author inPubMed Google Scholar
22. Gokul Ramaswami
    You can also search for this author inPubMed Google Scholar
23. Jinny Conte
    You can also search for this author inPubMed Google Scholar
24. Irma Lopez
    You can also search for this author inPubMed Google Scholar
25. Joseph Washburn
    You can also search for this author inPubMed Google Scholar
26. James MacDonald
    You can also search for this author inPubMed Google Scholar
27. Jinghua Hu
    You can also search for this author inPubMed Google Scholar
28. Yukiko Yamashita
    You can also search for this author inPubMed Google Scholar
29. Eamonn R Maher
    You can also search for this author inPubMed Google Scholar
30. Lisa M Guay-Woodford
    You can also search for this author inPubMed Google Scholar
31. Hartmut P H Neumann
    You can also search for this author inPubMed Google Scholar
32. Nicholas Obermüller
    You can also search for this author inPubMed Google Scholar
33. Robert K Koenekoop
    You can also search for this author inPubMed Google Scholar
34. Carsten Bergmann
    You can also search for this author inPubMed Google Scholar
35. Xiaoshu Bei
    You can also search for this author inPubMed Google Scholar
36. Richard A Lewis
    You can also search for this author inPubMed Google Scholar
37. Nicholas Katsanis
    You can also search for this author inPubMed Google Scholar
38. Vanda Lopes
    You can also search for this author inPubMed Google Scholar
39. David S Williams
    You can also search for this author inPubMed Google Scholar
40. Robert H Lyons
    You can also search for this author inPubMed Google Scholar
41. Chi V Dang
    You can also search for this author inPubMed Google Scholar
42. Daniela A Brito
    You can also search for this author inPubMed Google Scholar
43. Mónica Bettencourt Dias
    You can also search for this author inPubMed Google Scholar
44. Xinmin Zhang
    You can also search for this author inPubMed Google Scholar
45. James D Cavalcoli
    You can also search for this author inPubMed Google Scholar
46. Gudrun Nürnberg
    You can also search for this author inPubMed Google Scholar
47. Peter Nürnberg
    You can also search for this author inPubMed Google Scholar
48. Eric A Pierce
    You can also search for this author inPubMed Google Scholar
49. Peter K Jackson
    You can also search for this author inPubMed Google Scholar
50. Corinne Antignac
    You can also search for this author inPubMed Google Scholar
51. Sophie Saunier
    You can also search for this author inPubMed Google Scholar
52. Ronald Roepman
    You can also search for this author inPubMed Google Scholar
53. Helene Dollfus
    You can also search for this author inPubMed Google Scholar
54. Hemant Khanna
    You can also search for this author inPubMed Google Scholar
55. Friedhelm Hildebrandt
    You can also search for this author inPubMed 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 toFriedhelm Hildebrandt.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights 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: 19 April 2010
• Accepted: 18 August 2010
• Published: 12 September 2010
• Issue Date: October 2010
• DOI: https://doi.org/10.1038/ng.662