PUBLICATION
Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy
- Authors
- Otto, E.A., Hurd, T.W., Airik, R., Chaki, M., Zhou, W., Stoetzel, C., Patil, S.B., Levy, S., Ghosh, A.K., Murga-Zamalloa, C.A., van Reeuwijk, J., Letteboer, S.J., Sang, L., Giles, R.H., Liu, Q., Coene, K.L., Estrada-Cuzcano, A., Collin, R.W., McLaughlin, H.M., Held, S., Kasanuki, J.M., Ramaswami, G., Conte, J., Lopez, I., Washburn, J., Macdonald, J., Hu, J., Yamashita, Y., Maher, E.R., Guay-Woodford, L.M., Neumann, H.P., Obermüller, N., Koenekoop, R.K., Bergmann, C., Bei, X., Lewis, R.A., Katsanis, N., Lopes, V., Williams, D.S., Lyons, R.H., Dang, C.V., Brito, D.A., Dias, M.B., Zhang, X., Cavalcoli, J.D., Nürnberg, G., Nürnberg, P., Pierce, E.A., Jackson, P.K., Antignac, C., Saunier, S., Roepman, R., Dollfus, H., Khanna, H., and Hildebrandt, F.
- ID
- ZDB-PUB-100929-19
- Date
- 2010
- Source
- Nature Genetics 42(10): 840-850 (Journal)
- Registered Authors
- Bergmann, Carsten, Hildebrandt, Friedhelm, Katsanis, Nicholas, Khanna, Hemant, Liu, Qin, Zhou, Weibin
- Keywords
- none
- MeSH Terms
-
- Family
- Reverse Transcriptase Polymerase Chain Reaction
- RNA, Small Interfering/pharmacology
- Cyclic AMP/metabolism
- Fluorescent Antibody Technique, Indirect
- Two-Hybrid System Techniques
- Mutation/genetics*
- Rats
- Homozygote
- Subcellular Fractions
- Exons/genetics*
- Humans
- Autoantigens/genetics*
- Zebrafish/genetics
- Zebrafish/growth & development
- Blotting, Western
- Photoreceptor Cells, Vertebrate/metabolism
- Photoreceptor Cells, Vertebrate/ultrastructure
- Kidney Diseases/genetics*
- Kidney Diseases/pathology
- Animals
- Proteins/genetics
- Proteins/metabolism
- Neoplasm Proteins/antagonists & inhibitors
- Neoplasm Proteins/genetics*
- Gene Expression Regulation, Developmental
- Molecular Sequence Data
- Mice
- RNA, Messenger/genetics
- Case-Control Studies
- Retinal Diseases/genetics*
- Retinal Diseases/pathology
- Genetic Association Studies*
- Centrosome/metabolism
- PubMed
- 20835237 Full text @ Nat. Genet.
Citation
Otto, E.A., Hurd, T.W., Airik, R., Chaki, M., Zhou, W., Stoetzel, C., Patil, S.B., Levy, S., Ghosh, A.K., Murga-Zamalloa, C.A., van Reeuwijk, J., Letteboer, S.J., Sang, L., Giles, R.H., Liu, Q., Coene, K.L., Estrada-Cuzcano, A., Collin, R.W., McLaughlin, H.M., Held, S., Kasanuki, J.M., Ramaswami, G., Conte, J., Lopez, I., Washburn, J., Macdonald, J., Hu, J., Yamashita, Y., Maher, E.R., Guay-Woodford, L.M., Neumann, H.P., Obermüller, N., Koenekoop, R.K., Bergmann, C., Bei, X., Lewis, R.A., Katsanis, N., Lopes, V., Williams, D.S., Lyons, R.H., Dang, C.V., Brito, D.A., Dias, M.B., Zhang, X., Cavalcoli, J.D., Nürnberg, G., Nürnberg, P., Pierce, E.A., Jackson, P.K., Antignac, C., Saunier, S., Roepman, R., Dollfus, H., Khanna, H., and Hildebrandt, F. (2010) Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nature Genetics. 42(10):840-850.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping