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

Edgar A Otto, Toby W Hurd, Rannar Airik, Moumita Chaki, Weibin Zhou, Corinne Stoetzel, Suresh B Patil, Shawn Levy, Amiya K Ghosh, Carlos A Murga-Zamalloa, Jeroen van Reeuwijk, Stef J F Letteboer, Liyun Sang, Rachel H Giles, Qin Liu, Karlien L M Coene, Alejandro Estrada-Cuzcano, Rob W J Collin, Heather M McLaughlin, Susanne HeldJennifer M Kasanuki, Gokul Ramaswami, Jinny Conte, Irma Lopez, Joseph Washburn, James Macdonald, Jinghua Hu, Yukiko Yamashita, Eamonn R Maher, Lisa M Guay-Woodford, Hartmut P H Neumann, Nicholas Obermüller, Robert K Koenekoop, Carsten Bergmann, Xiaoshu Bei, Richard A Lewis, Nicholas Katsanis, Vanda Lopes, David S Williams, Robert H Lyons, Chi V Dang, Daniela A Brito, Mónica Bettencourt Dias, Xinmin Zhang, James D Cavalcoli, Gudrun Nürnberg, Peter Nürnberg, Eric A Pierce, Peter K Jackson, Corinne Antignac, Sophie Saunier, Ronald Roepman, Helene Dollfus, Hemant Khanna, Friedhelm Hildebrandt

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)840-850
Number of pages11
JournalNature Genetics
Issue number10
Publication statusPublished - Oct 2010


  • Animals
  • Humans
  • Two-Hybrid System Techniques
  • RNA, Small Interfering
  • Centrosome
  • Rats
  • Molecular Sequence Data
  • Kidney Diseases
  • Retinal Diseases
  • Homozygote
  • Fluorescent Antibody Technique, Indirect
  • Exons
  • Cyclic AMP
  • Genetic Association Studies
  • Subcellular Fractions
  • Mice
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish
  • Autoantigens
  • RNA, Messenger
  • Blotting, Western
  • Neoplasm Proteins
  • Case-Control Studies
  • Family
  • Proteins
  • Mutation
  • Gene Expression Regulation, Developmental
  • Photoreceptor Cells, Vertebrate

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