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

E.A. Otto; T.W. Hurd; R. Airik; M. Chaki; W. Zhou; C. Stoetzel; S.B. Patil; S. Levy; A.K. Ghosh; C.A. Murga-Zamalloa; J. van Reeuwijk; S.J. Letteboer; L. Sang; R.H. Giles; Q. Liu; K.L. Coene; A. Estrada-Cuzcano; R.W. Collin; H.M. McLaughlin; S. Held; J.M. Kasanuki; G. Ramaswami; J. Conte; I. Lopez; J. Washburn; J. Macdonald; J. Hu; Y. Yamashita; ER Maher; L.M. Guay-Woodford; H.P. Neumann; N. Obermuller; R.K. Koenekoop; C. Bergmann; X. Bei; R.A. Lewis; N. Katsanis; V. Lopes; D.S. Williams; R.H. Lyons; C.V. Dang; D.A. Brito; M.B. Dias; X. Zhang; J.D. Cavalcoli; G. Nurnberg; P. Nurnberg; E.A. Pierce; P.K. Jackson; C. Antignac; S. Saunier; R. Roepman; H. Dollfus; H. Khanna; F. Hildebrandt

doi:10.1038/ng.662

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

E.A. Otto, T.W. Hurd, R. Airik, M. Chaki, W. Zhou, C. Stoetzel, S.B. Patil, S. Levy, A.K. Ghosh, C.A. Murga-Zamalloa, J. van Reeuwijk, S.J. Letteboer, L. Sang, R.H. Giles, Q. Liu, K.L. Coene, A. Estrada-Cuzcano, R.W. Collin, H.M. McLaughlin, S. HeldJ.M. Kasanuki, G. Ramaswami, J. Conte, I. Lopez, J. Washburn, J. Macdonald, J. Hu, Y. Yamashita, ER Maher, L.M. Guay-Woodford, H.P. Neumann, N. Obermuller, R.K. Koenekoop, C. Bergmann, X. Bei, R.A. Lewis, N. Katsanis, V. Lopes, D.S. Williams, R.H. Lyons, C.V. Dang, D.A. Brito, M.B. Dias, X. Zhang, J.D. Cavalcoli, G. Nurnberg, P. Nurnberg, E.A. Pierce, P.K. Jackson, C. Antignac, S. Saunier, R. Roepman, H. Dollfus, H. Khanna, F. Hildebrandt

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	840-850
Number of pages	11
Journal	Nature Genetics
Volume	42
Issue number	10
DOIs	https://doi.org/10.1038/ng.662
Publication status	Published - 2010

Keywords

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

Access to Document

10.1038/ng.662

Cite this

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., ... Hildebrandt, F. (2010). Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nature Genetics, 42(10), 840-850. https://doi.org/10.1038/ng.662

@article{b8ef5a524ab94c51b0d3045b8f80b469,

title = "Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy",

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.",

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

author = "E.A. Otto and T.W. Hurd and R. Airik and M. Chaki and W. Zhou and C. Stoetzel and S.B. Patil and S. Levy and A.K. Ghosh and C.A. Murga-Zamalloa and {van Reeuwijk}, J. and S.J. Letteboer and L. Sang and R.H. Giles and Q. Liu and K.L. Coene and A. Estrada-Cuzcano and R.W. Collin and H.M. McLaughlin and S. Held and J.M. Kasanuki and G. Ramaswami and J. Conte and I. Lopez and J. Washburn and J. Macdonald and J. Hu and Y. Yamashita and ER Maher and L.M. Guay-Woodford and H.P. Neumann and N. Obermuller and R.K. Koenekoop and C. Bergmann and X. Bei and R.A. Lewis and N. Katsanis and V. Lopes and D.S. Williams and R.H. Lyons and C.V. Dang and D.A. Brito and M.B. Dias and X. Zhang and J.D. Cavalcoli and G. Nurnberg and P. Nurnberg and E.A. Pierce and P.K. Jackson and C. Antignac and S. Saunier and R. Roepman and H. Dollfus and H. Khanna and F. Hildebrandt",

year = "2010",

doi = "10.1038/ng.662",

language = "English",

volume = "42",

pages = "840--850",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

}

Otto, EA, Hurd, TW, Airik, R, Chaki, M, Zhou, W, Stoetzel, C, Patil, SB, Levy, S, Ghosh, AK, Murga-Zamalloa, CA, van Reeuwijk, J, Letteboer, SJ, Sang, L, Giles, RH, Liu, Q, Coene, KL, Estrada-Cuzcano, A, Collin, RW, McLaughlin, HM, Held, S, Kasanuki, JM, Ramaswami, G, Conte, J, Lopez, I, Washburn, J, Macdonald, J, Hu, J, Yamashita, Y, Maher, ER, Guay-Woodford, LM, Neumann, HP, Obermuller, N, Koenekoop, RK, Bergmann, C, Bei, X, Lewis, RA, Katsanis, N, Lopes, V, Williams, DS, Lyons, RH, Dang, CV, Brito, DA, Dias, MB, Zhang, X, Cavalcoli, JD, Nurnberg, G, Nurnberg, P, Pierce, EA, Jackson, PK, Antignac, C, Saunier, S, Roepman, R, Dollfus, H, Khanna, H & Hildebrandt, F 2010, 'Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy', Nature Genetics, vol. 42, no. 10, pp. 840-850. https://doi.org/10.1038/ng.662

TY - JOUR

T1 - Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy

AU - Otto, E.A.

AU - Hurd, T.W.

AU - Airik, R.

AU - Chaki, M.

AU - Zhou, W.

AU - Stoetzel, C.

AU - Patil, S.B.

AU - Levy, S.

AU - Ghosh, A.K.

AU - Murga-Zamalloa, C.A.

AU - van Reeuwijk, J.

AU - Letteboer, S.J.

AU - Sang, L.

AU - Giles, R.H.

AU - Liu, Q.

AU - Coene, K.L.

AU - Estrada-Cuzcano, A.

AU - Collin, R.W.

AU - McLaughlin, H.M.

AU - Held, S.

AU - Kasanuki, J.M.

AU - Ramaswami, G.

AU - Conte, J.

AU - Lopez, I.

AU - Washburn, J.

AU - Macdonald, J.

AU - Hu, J.

AU - Yamashita, Y.

AU - Maher, ER

AU - Guay-Woodford, L.M.

AU - Neumann, H.P.

AU - Obermuller, N.

AU - Koenekoop, R.K.

AU - Bergmann, C.

AU - Bei, X.

AU - Lewis, R.A.

AU - Katsanis, N.

AU - Lopes, V.

AU - Williams, D.S.

AU - Lyons, R.H.

AU - Dang, C.V.

AU - Brito, D.A.

AU - Dias, M.B.

AU - Zhang, X.

AU - Cavalcoli, J.D.

AU - Nurnberg, G.

AU - Nurnberg, P.

AU - Pierce, E.A.

AU - Jackson, P.K.

AU - Antignac, C.

AU - Saunier, S.

AU - Roepman, R.

AU - Dollfus, H.

AU - Khanna, H.

AU - Hildebrandt, F.

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Animals

KW - Autoantigens

KW - Blotting, Western

KW - Case-Control Studies

KW - Centrosome

KW - Cyclic AMP

KW - Exons

KW - Family

KW - Fluorescent Antibody Technique, Indirect

KW - Gene Expression Regulation, Developmental

KW - Genetic Association Studies

KW - Homozygote

KW - Humans

KW - Kidney Diseases

KW - Mice

KW - Molecular Sequence Data

KW - Mutation

KW - Neoplasm Proteins

KW - Photoreceptor Cells, Vertebrate

KW - Proteins

KW - RNA, Messenger

KW - RNA, Small Interfering

KW - Rats

KW - Retinal Diseases

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Subcellular Fractions

KW - Two-Hybrid System Techniques

KW - Zebrafish

U2 - 10.1038/ng.662

DO - 10.1038/ng.662

M3 - Article

C2 - 20835237

SN - 1061-4036

VL - 42

SP - 840

EP - 850

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this