22 results on '"Nijman IJ"'
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Search Results
2. De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia
- Author
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Stokman, M.F., Oud, M.M., Binsbergen, E. van, Slaats, G.G., Nicolaou, N., Renkema, K.Y., Nijman, IJ, Roepman, R., Giles, R.H., Arts, H.H., Knoers, N.V.A.M., Haelst, M.M. van, Stokman, M.F., Oud, M.M., Binsbergen, E. van, Slaats, G.G., Nicolaou, N., Renkema, K.Y., Nijman, IJ, Roepman, R., Giles, R.H., Arts, H.H., Knoers, N.V.A.M., and Haelst, M.M. van
- Abstract
Item does not contain fulltext, We report an 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. Array comparative genomic hybridization analysis identified a de novo 4.5-Mb microdeletion on chromosome 14q24.2q24.3. The deleted region and phenotype partially overlap with previously reported patients. Here, we provide an overview of the literature on 14q24 microdeletions and further delineate the associated phenotype. We performed exome sequencing to examine other causes for the phenotype and queried genes present in the 14q24.2q24.3 microdeletion that are associated with recessive disease for variants in the non-deleted allele. The deleted region contains 65 protein-coding genes, including the ciliary gene IFT43. Although Sanger and exome sequencing did not identify variants in the second IFT43 allele or in other IFT complex A-protein-encoding genes, immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport. This could suggest a ciliary defect in the pathogenesis of this disorder. (c) 2016 Wiley Periodicals, Inc.
- Published
- 2016
3. Prioritization and burden analysis of rare variants in 208 candidate genes suggest they do not play a major role in CAKUT
- Author
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Nicolaou, N., Pulit, S.L., Nijman, IJ, Monroe, G.R., Feitz, W.F.J., Schreuder, M.F., Eerde, A.M. van, Jong, T.P. de, Giltay, J.C., Zwaag, B. van der, Havenith, M.R., Zwakenberg, S., Zanden, L.F.M. van der, Poelmans, G.J.V., Cornelissen, E.A.M., Lilien, M.R., Franke, B., Roeleveld, N., Rooij, I.A.L.M. van, Cuppen, E., Bongers, E.M.H.F., Giles, R.H., Knoers, N.V.A.M., Renkema, K.Y., Nicolaou, N., Pulit, S.L., Nijman, IJ, Monroe, G.R., Feitz, W.F.J., Schreuder, M.F., Eerde, A.M. van, Jong, T.P. de, Giltay, J.C., Zwaag, B. van der, Havenith, M.R., Zwakenberg, S., Zanden, L.F.M. van der, Poelmans, G.J.V., Cornelissen, E.A.M., Lilien, M.R., Franke, B., Roeleveld, N., Rooij, I.A.L.M. van, Cuppen, E., Bongers, E.M.H.F., Giles, R.H., Knoers, N.V.A.M., and Renkema, K.Y.
- Abstract
Item does not contain fulltext, The leading cause of end-stage renal disease in children is attributed to congenital anomalies of the kidney and urinary tract (CAKUT). Familial clustering and mouse models support the presence of monogenic causes. Genetic testing is insufficient as it mainly focuses on HNF1B and PAX2 mutations that are thought to explain CAKUT in 5-15% of patients. To identify novel, potentially pathogenic variants in additional genes, we designed a panel of genes identified from studies on familial forms of isolated or syndromic CAKUT and genes suggested by in vitro and in vivo CAKUT models. The coding exons of 208 genes were analyzed in 453 patients with CAKUT using next-generation sequencing. Rare truncating, splice-site variants, and non-synonymous variants, predicted to be deleterious and conserved, were prioritized as the most promising variants to have an effect on CAKUT. Previously reported disease-causing mutations were detected, but only five were fully penetrant causal mutations that improved diagnosis. We prioritized 148 candidate variants in 151 patients, found in 82 genes, for follow-up studies. Using a burden test, no significant excess of rare variants in any of the genes in our cohort compared with controls was found. Thus, in a study representing the largest set of genes analyzed in CAKUT patients to date, the contribution of previously implicated genes to CAKUT risk was significantly smaller than expected, and the disease may be more complex than previously assumed.
- Published
- 2016
4. De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia
- Author
-
Stokman, M.F., Oud, M.M., Binsbergen, E. van, Slaats, G.G., Nicolaou, N., Renkema, K.Y., Nijman, IJ, Roepman, R., Giles, R.H., Arts, H.H., Knoers, N.V.A.M., Haelst, M.M. van, Stokman, M.F., Oud, M.M., Binsbergen, E. van, Slaats, G.G., Nicolaou, N., Renkema, K.Y., Nijman, IJ, Roepman, R., Giles, R.H., Arts, H.H., Knoers, N.V.A.M., and Haelst, M.M. van
- Abstract
Item does not contain fulltext, We report an 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. Array comparative genomic hybridization analysis identified a de novo 4.5-Mb microdeletion on chromosome 14q24.2q24.3. The deleted region and phenotype partially overlap with previously reported patients. Here, we provide an overview of the literature on 14q24 microdeletions and further delineate the associated phenotype. We performed exome sequencing to examine other causes for the phenotype and queried genes present in the 14q24.2q24.3 microdeletion that are associated with recessive disease for variants in the non-deleted allele. The deleted region contains 65 protein-coding genes, including the ciliary gene IFT43. Although Sanger and exome sequencing did not identify variants in the second IFT43 allele or in other IFT complex A-protein-encoding genes, immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport. This could suggest a ciliary defect in the pathogenesis of this disorder. (c) 2016 Wiley Periodicals, Inc.
- Published
- 2016
5. Prioritization and burden analysis of rare variants in 208 candidate genes suggest they do not play a major role in CAKUT
- Author
-
Nicolaou, N., Pulit, S.L., Nijman, IJ, Monroe, G.R., Feitz, W.F.J., Schreuder, M.F., Eerde, A.M. van, Jong, T.P. de, Giltay, J.C., Zwaag, B. van der, Havenith, M.R., Zwakenberg, S., Zanden, L.F.M. van der, Poelmans, G.J.V., Cornelissen, E.A.M., Lilien, M.R., Franke, B., Roeleveld, N., Rooij, I.A.L.M. van, Cuppen, E., Bongers, E.M.H.F., Giles, R.H., Knoers, N.V.A.M., Renkema, K.Y., Nicolaou, N., Pulit, S.L., Nijman, IJ, Monroe, G.R., Feitz, W.F.J., Schreuder, M.F., Eerde, A.M. van, Jong, T.P. de, Giltay, J.C., Zwaag, B. van der, Havenith, M.R., Zwakenberg, S., Zanden, L.F.M. van der, Poelmans, G.J.V., Cornelissen, E.A.M., Lilien, M.R., Franke, B., Roeleveld, N., Rooij, I.A.L.M. van, Cuppen, E., Bongers, E.M.H.F., Giles, R.H., Knoers, N.V.A.M., and Renkema, K.Y.
- Abstract
Contains fulltext : 168068.pdf (Publisher’s version ) (Closed access), The leading cause of end-stage renal disease in children is attributed to congenital anomalies of the kidney and urinary tract (CAKUT). Familial clustering and mouse models support the presence of monogenic causes. Genetic testing is insufficient as it mainly focuses on HNF1B and PAX2 mutations that are thought to explain CAKUT in 5-15% of patients. To identify novel, potentially pathogenic variants in additional genes, we designed a panel of genes identified from studies on familial forms of isolated or syndromic CAKUT and genes suggested by in vitro and in vivo CAKUT models. The coding exons of 208 genes were analyzed in 453 patients with CAKUT using next-generation sequencing. Rare truncating, splice-site variants, and non-synonymous variants, predicted to be deleterious and conserved, were prioritized as the most promising variants to have an effect on CAKUT. Previously reported disease-causing mutations were detected, but only five were fully penetrant causal mutations that improved diagnosis. We prioritized 148 candidate variants in 151 patients, found in 82 genes, for follow-up studies. Using a burden test, no significant excess of rare variants in any of the genes in our cohort compared with controls was found. Thus, in a study representing the largest set of genes analyzed in CAKUT patients to date, the contribution of previously implicated genes to CAKUT risk was significantly smaller than expected, and the disease may be more complex than previously assumed.
- Published
- 2016
6. De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia
- Author
-
Stokman, M.F., Oud, M.M., Binsbergen, E. van, Slaats, G.G., Nicolaou, N., Renkema, K.Y., Nijman, IJ, Roepman, R., Giles, R.H., Arts, H.H., Knoers, N.V.A.M., Haelst, M.M. van, Stokman, M.F., Oud, M.M., Binsbergen, E. van, Slaats, G.G., Nicolaou, N., Renkema, K.Y., Nijman, IJ, Roepman, R., Giles, R.H., Arts, H.H., Knoers, N.V.A.M., and Haelst, M.M. van
- Abstract
Item does not contain fulltext, We report an 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. Array comparative genomic hybridization analysis identified a de novo 4.5-Mb microdeletion on chromosome 14q24.2q24.3. The deleted region and phenotype partially overlap with previously reported patients. Here, we provide an overview of the literature on 14q24 microdeletions and further delineate the associated phenotype. We performed exome sequencing to examine other causes for the phenotype and queried genes present in the 14q24.2q24.3 microdeletion that are associated with recessive disease for variants in the non-deleted allele. The deleted region contains 65 protein-coding genes, including the ciliary gene IFT43. Although Sanger and exome sequencing did not identify variants in the second IFT43 allele or in other IFT complex A-protein-encoding genes, immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport. This could suggest a ciliary defect in the pathogenesis of this disorder. (c) 2016 Wiley Periodicals, Inc.
- Published
- 2016
7. Next-generation sequencing-based genome diagnostics across clinical genetics centers: implementation choices and their effects
- Author
-
Vrijenhoek, T., Kraaijeveld, K., Elferink, M., Ligt, J. de, Kranendonk, E., Santen, G., Nijman, IJ, Butler, D., Claes, G., Costessi, A., Dorlijn, W., Eyndhoven, W. van, Halley, D.J., Hout, M.C. van den, Hove, S. van, Johansson, L.F., Jongbloed, J.D., Kamps, R., Kockx, C.E., Koning, B. de, Kriek, M., Deprez, R.L., Lunstroo, H., Mannens, M., Mook, O.R., Nelen, M.R., Ploem, C., Rijnen, M., Saris, J.J., Sinke, R., Sistermans, E., Slegtenhorst, M. van, Sleutels, F., Stoep, N. van der, Tienhoven, M. van, Vermaat, M., Vogel, M., Waisfisz, Q., Weiss, J.M., Wijngaard, A. van den, Workum, W. van, IJntema, H., Zwaag, B. van der, van, I.W.F., Dunnen, J.T. den, Veltman, J.A., Hennekam, R., Cuppen, E., Vrijenhoek, T., Kraaijeveld, K., Elferink, M., Ligt, J. de, Kranendonk, E., Santen, G., Nijman, IJ, Butler, D., Claes, G., Costessi, A., Dorlijn, W., Eyndhoven, W. van, Halley, D.J., Hout, M.C. van den, Hove, S. van, Johansson, L.F., Jongbloed, J.D., Kamps, R., Kockx, C.E., Koning, B. de, Kriek, M., Deprez, R.L., Lunstroo, H., Mannens, M., Mook, O.R., Nelen, M.R., Ploem, C., Rijnen, M., Saris, J.J., Sinke, R., Sistermans, E., Slegtenhorst, M. van, Sleutels, F., Stoep, N. van der, Tienhoven, M. van, Vermaat, M., Vogel, M., Waisfisz, Q., Weiss, J.M., Wijngaard, A. van den, Workum, W. van, IJntema, H., Zwaag, B. van der, van, I.W.F., Dunnen, J.T. den, Veltman, J.A., Hennekam, R., and Cuppen, E.
- Abstract
Item does not contain fulltext
- Published
- 2015
8. Myeloid lineage-restricted somatic mosaicism of NLRP3 mutations in patients with variant Schnitzler syndrome
- Author
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Koning, H.D. de, Gijn, M.E. van, Stoffels, M., Jongekrijg, J., Zeeuwen, P.L.J.M., Elferink, M.G., Nijman, IJ, Jansen, P.A.M., Neveling, K., Meer, J.W.M. van der, Schalkwijk, J., Simon, A., Koning, H.D. de, Gijn, M.E. van, Stoffels, M., Jongekrijg, J., Zeeuwen, P.L.J.M., Elferink, M.G., Nijman, IJ, Jansen, P.A.M., Neveling, K., Meer, J.W.M. van der, Schalkwijk, J., and Simon, A.
- Abstract
Contains fulltext : 153462.pdf (publisher's version ) (Closed access)
- Published
- 2015
9. Next-generation sequencing-based genome diagnostics across clinical genetics centers: implementation choices and their effects
- Author
-
Vrijenhoek, T., Kraaijeveld, K., Elferink, M., Ligt, J. de, Kranendonk, E., Santen, G., Nijman, IJ, Butler, D., Claes, G., Costessi, A., Dorlijn, W., Eyndhoven, W. van, Halley, D.J., Hout, M.C. van den, Hove, S. van, Johansson, L.F., Jongbloed, J.D., Kamps, R., Kockx, C.E., Koning, B. de, Kriek, M., Deprez, R.L., Lunstroo, H., Mannens, M., Mook, O.R., Nelen, M.R., Ploem, C., Rijnen, M., Saris, J.J., Sinke, R., Sistermans, E., Slegtenhorst, M. van, Sleutels, F., Stoep, N. van der, Tienhoven, M. van, Vermaat, M., Vogel, M., Waisfisz, Q., Weiss, J.M., Wijngaard, A. van den, Workum, W. van, IJntema, H., Zwaag, B. van der, van, I.W.F., Dunnen, J.T. den, Veltman, J.A., Hennekam, R., Cuppen, E., Vrijenhoek, T., Kraaijeveld, K., Elferink, M., Ligt, J. de, Kranendonk, E., Santen, G., Nijman, IJ, Butler, D., Claes, G., Costessi, A., Dorlijn, W., Eyndhoven, W. van, Halley, D.J., Hout, M.C. van den, Hove, S. van, Johansson, L.F., Jongbloed, J.D., Kamps, R., Kockx, C.E., Koning, B. de, Kriek, M., Deprez, R.L., Lunstroo, H., Mannens, M., Mook, O.R., Nelen, M.R., Ploem, C., Rijnen, M., Saris, J.J., Sinke, R., Sistermans, E., Slegtenhorst, M. van, Sleutels, F., Stoep, N. van der, Tienhoven, M. van, Vermaat, M., Vogel, M., Waisfisz, Q., Weiss, J.M., Wijngaard, A. van den, Workum, W. van, IJntema, H., Zwaag, B. van der, van, I.W.F., Dunnen, J.T. den, Veltman, J.A., Hennekam, R., and Cuppen, E.
- Abstract
Item does not contain fulltext
- Published
- 2015
10. Myeloid lineage-restricted somatic mosaicism of NLRP3 mutations in patients with variant Schnitzler syndrome
- Author
-
Koning, H.D. de, Gijn, M.E. van, Stoffels, M., Jongekrijg, J., Zeeuwen, P.L.J.M., Elferink, M.G., Nijman, IJ, Jansen, P.A.M., Neveling, K., Meer, J.W.M. van der, Schalkwijk, J., Simon, A., Koning, H.D. de, Gijn, M.E. van, Stoffels, M., Jongekrijg, J., Zeeuwen, P.L.J.M., Elferink, M.G., Nijman, IJ, Jansen, P.A.M., Neveling, K., Meer, J.W.M. van der, Schalkwijk, J., and Simon, A.
- Abstract
Contains fulltext : 153462.pdf (publisher's version ) (Closed access)
- Published
- 2015
11. Next-generation sequencing-based genome diagnostics across clinical genetics centers: implementation choices and their effects
- Author
-
Vrijenhoek, T., Kraaijeveld, K., Elferink, M., Ligt, J. de, Kranendonk, E., Santen, G., Nijman, IJ, Butler, D., Claes, G., Costessi, A., Dorlijn, W., Eyndhoven, W. van, Halley, D.J., Hout, M.C. van den, Hove, S. van, Johansson, L.F., Jongbloed, J.D., Kamps, R., Kockx, C.E., Koning, B. de, Kriek, M., Deprez, R.L., Lunstroo, H., Mannens, M., Mook, O.R., Nelen, M.R., Ploem, C., Rijnen, M., Saris, J.J., Sinke, R., Sistermans, E., Slegtenhorst, M. van, Sleutels, F., Stoep, N. van der, Tienhoven, M. van, Vermaat, M., Vogel, M., Waisfisz, Q., Weiss, J.M., Wijngaard, A. van den, Workum, W. van, IJntema, H., Zwaag, B. van der, van, I.W.F., Dunnen, J.T. den, Veltman, J.A., Hennekam, R., Cuppen, E., Vrijenhoek, T., Kraaijeveld, K., Elferink, M., Ligt, J. de, Kranendonk, E., Santen, G., Nijman, IJ, Butler, D., Claes, G., Costessi, A., Dorlijn, W., Eyndhoven, W. van, Halley, D.J., Hout, M.C. van den, Hove, S. van, Johansson, L.F., Jongbloed, J.D., Kamps, R., Kockx, C.E., Koning, B. de, Kriek, M., Deprez, R.L., Lunstroo, H., Mannens, M., Mook, O.R., Nelen, M.R., Ploem, C., Rijnen, M., Saris, J.J., Sinke, R., Sistermans, E., Slegtenhorst, M. van, Sleutels, F., Stoep, N. van der, Tienhoven, M. van, Vermaat, M., Vogel, M., Waisfisz, Q., Weiss, J.M., Wijngaard, A. van den, Workum, W. van, IJntema, H., Zwaag, B. van der, van, I.W.F., Dunnen, J.T. den, Veltman, J.A., Hennekam, R., and Cuppen, E.
- Abstract
Item does not contain fulltext
- Published
- 2015
12. Myeloid lineage-restricted somatic mosaicism of NLRP3 mutations in patients with variant Schnitzler syndrome
- Author
-
Koning, H.D. de, Gijn, M.E. van, Stoffels, M., Jongekrijg, J., Zeeuwen, P.L.J.M., Elferink, M.G., Nijman, IJ, Jansen, P.A.M., Neveling, K., Meer, J.W.M. van der, Schalkwijk, J., Simon, A., Koning, H.D. de, Gijn, M.E. van, Stoffels, M., Jongekrijg, J., Zeeuwen, P.L.J.M., Elferink, M.G., Nijman, IJ, Jansen, P.A.M., Neveling, K., Meer, J.W.M. van der, Schalkwijk, J., and Simon, A.
- Abstract
Contains fulltext : 153462.pdf (publisher's version ) (Closed access)
- Published
- 2015
13. Next-generation sequencing-based genome diagnostics across clinical genetics centers: implementation choices and their effects
- Author
-
Vrijenhoek, T, Kraaijeveld, K, Elferink, M, de Ligt, J, Kranendonk, E, Santen, G, Nijman, IJ, Butler, D, Claes, G, Costessi, A, Dorlijn, W, van Eyndhoven, W, Halley, Dicky, Van den Hout - van Vroonhoven, Mirjam, van Hove, S, Johansson, LF, Jongbloed, JDH, Kamps, R, Kockx, Christel, de Koning, B, Kriek, M, Deprez, RLD, Lunstroo, H, Mannens, M, Mook, OR, Nelen, M, Ploem, C, Rijnen, M, Saris, Jasper, Sinke, R, Sistermans, E, van Slegtenhorst, Marjon, Sleutels, Frank, van der Stoep, N, Tienhoven, Marianne, Vermaat, M, Vogel, M, Waisfisz, Q, Weiss, JM, van den Wijngaard, A, van Workum, W, Ijntema, H, Van der Zwaag, B, van Ijcken, Wilfred, den Dunnen, J, Veltman, JA, Hennekam, R, Cuppen, E, Vrijenhoek, T, Kraaijeveld, K, Elferink, M, de Ligt, J, Kranendonk, E, Santen, G, Nijman, IJ, Butler, D, Claes, G, Costessi, A, Dorlijn, W, van Eyndhoven, W, Halley, Dicky, Van den Hout - van Vroonhoven, Mirjam, van Hove, S, Johansson, LF, Jongbloed, JDH, Kamps, R, Kockx, Christel, de Koning, B, Kriek, M, Deprez, RLD, Lunstroo, H, Mannens, M, Mook, OR, Nelen, M, Ploem, C, Rijnen, M, Saris, Jasper, Sinke, R, Sistermans, E, van Slegtenhorst, Marjon, Sleutels, Frank, van der Stoep, N, Tienhoven, Marianne, Vermaat, M, Vogel, M, Waisfisz, Q, Weiss, JM, van den Wijngaard, A, van Workum, W, Ijntema, H, Van der Zwaag, B, van Ijcken, Wilfred, den Dunnen, J, Veltman, JA, Hennekam, R, and Cuppen, E
- Abstract
Implementation of next-generation DNA sequencing (NGS) technology into routine diagnostic genome care requires strategic choices. Instead of theoretical discussions on the consequences of such choices, we compared NGS-based diagnostic practices in eight clinical genetic centers in the Netherlands, based on genetic testing of nine pre-selected patients with cardiomyopathy. We highlight critical implementation choices, including the specific contributions of laboratory and medical specialists, bioinformaticians and researchers to diagnostic genome care, and how these affect interpretation and reporting of variants. Reported pathogenic mutations were consistent for all but one patient. Of the two centers that were inconsistent in their diagnosis, one reported to have found 'no causal variant', thereby underdiagnosing this patient. The other provided an alternative diagnosis, identifying another variant as causal than the other centers. Ethical and legal analysis showed that informed consent procedures in all centers were generally adequate for diagnostic NGS applications that target a limited set of genes, but not for exome-and genome-based diagnosis. We propose changes to further improve and align these procedures, taking into account the blurring boundary between diagnostics and research, and specific counseling options for exome- and genome-based diagnostics. We conclude that alternative diagnoses may infer a certain level of 'greediness' to come to a positive diagnosis in interpreting sequencing results. Moreover, there is an increasing interdependence of clinic, diagnostics and research departments for comprehensive diagnostic genome care. Therefore, we invite clinical geneticists, physicians, researchers, bioinformatics experts and patients to reconsider their role and position in future diagnostic genome care.
- Published
- 2015
14. Dominant missense mutations in ABCC9 cause Cantu syndrome.
- Author
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Harakalova, M., Harssel, J.J. van, Terhal, P.A., Lieshout, S. van, Duran, K., Renkens, I., Amor, D.J., Wilson, L.C., Kirk, E.P., Turner, C.L., Shears, D., Garcia-Minaur, S., Lees, M.M., Ross, A., Venselaar, H., Vriend, G., Takanari, H., Rook, M.B., Heyden, M.A. van der, Asselbergs, F.W., Breur, H.M., Swinkels, M.E., Scurr, I.J., Smithson, S.F., Knoers, N.V.A.M., Smagt, J.J. van der, Nijman, IJ, Kloosterman, W.P., Haelst, M.M. van, Haaften, G. van, Cuppen, E., Harakalova, M., Harssel, J.J. van, Terhal, P.A., Lieshout, S. van, Duran, K., Renkens, I., Amor, D.J., Wilson, L.C., Kirk, E.P., Turner, C.L., Shears, D., Garcia-Minaur, S., Lees, M.M., Ross, A., Venselaar, H., Vriend, G., Takanari, H., Rook, M.B., Heyden, M.A. van der, Asselbergs, F.W., Breur, H.M., Swinkels, M.E., Scurr, I.J., Smithson, S.F., Knoers, N.V.A.M., Smagt, J.J. van der, Nijman, IJ, Kloosterman, W.P., Haelst, M.M. van, Haaften, G. van, and Cuppen, E.
- Abstract
Item does not contain fulltext, Cantu syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals with Cantu syndrome examined. The ABCC9 protein is part of an ATP-dependent potassium (K(ATP)) channel that couples the metabolic state of a cell with its electrical activity. All mutations altered amino acids in or close to the transmembrane domains of ABCC9. Using electrophysiological measurements, we show that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. Moreover, similarities between the phenotype of individuals with Cantu syndrome and side effects from the K(ATP) channel agonist minoxidil indicate that the mutations in ABCC9 result in channel opening. Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantu syndrome.
- Published
- 2012
15. Dominant missense mutations in ABCC9 cause Cantu syndrome.
- Author
-
Harakalova, M., Harssel, J.J. van, Terhal, P.A., Lieshout, S. van, Duran, K., Renkens, I., Amor, D.J., Wilson, L.C., Kirk, E.P., Turner, C.L., Shears, D., Garcia-Minaur, S., Lees, M.M., Ross, A., Venselaar, H., Vriend, G., Takanari, H., Rook, M.B., Heyden, M.A. van der, Asselbergs, F.W., Breur, H.M., Swinkels, M.E., Scurr, I.J., Smithson, S.F., Knoers, N.V.A.M., Smagt, J.J. van der, Nijman, IJ, Kloosterman, W.P., Haelst, M.M. van, Haaften, G. van, Cuppen, E., Harakalova, M., Harssel, J.J. van, Terhal, P.A., Lieshout, S. van, Duran, K., Renkens, I., Amor, D.J., Wilson, L.C., Kirk, E.P., Turner, C.L., Shears, D., Garcia-Minaur, S., Lees, M.M., Ross, A., Venselaar, H., Vriend, G., Takanari, H., Rook, M.B., Heyden, M.A. van der, Asselbergs, F.W., Breur, H.M., Swinkels, M.E., Scurr, I.J., Smithson, S.F., Knoers, N.V.A.M., Smagt, J.J. van der, Nijman, IJ, Kloosterman, W.P., Haelst, M.M. van, Haaften, G. van, and Cuppen, E.
- Abstract
Item does not contain fulltext, Cantu syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals with Cantu syndrome examined. The ABCC9 protein is part of an ATP-dependent potassium (K(ATP)) channel that couples the metabolic state of a cell with its electrical activity. All mutations altered amino acids in or close to the transmembrane domains of ABCC9. Using electrophysiological measurements, we show that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. Moreover, similarities between the phenotype of individuals with Cantu syndrome and side effects from the K(ATP) channel agonist minoxidil indicate that the mutations in ABCC9 result in channel opening. Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantu syndrome.
- Published
- 2012
16. Dominant missense mutations in ABCC9 cause Cantu syndrome.
- Author
-
Harakalova, M., Harssel, J.J. van, Terhal, P.A., Lieshout, S. van, Duran, K., Renkens, I., Amor, D.J., Wilson, L.C., Kirk, E.P., Turner, C.L., Shears, D., Garcia-Minaur, S., Lees, M.M., Ross, A., Venselaar, H., Vriend, G., Takanari, H., Rook, M.B., Heyden, M.A. van der, Asselbergs, F.W., Breur, H.M., Swinkels, M.E., Scurr, I.J., Smithson, S.F., Knoers, N.V.A.M., Smagt, J.J. van der, Nijman, IJ, Kloosterman, W.P., Haelst, M.M. van, Haaften, G. van, Cuppen, E., Harakalova, M., Harssel, J.J. van, Terhal, P.A., Lieshout, S. van, Duran, K., Renkens, I., Amor, D.J., Wilson, L.C., Kirk, E.P., Turner, C.L., Shears, D., Garcia-Minaur, S., Lees, M.M., Ross, A., Venselaar, H., Vriend, G., Takanari, H., Rook, M.B., Heyden, M.A. van der, Asselbergs, F.W., Breur, H.M., Swinkels, M.E., Scurr, I.J., Smithson, S.F., Knoers, N.V.A.M., Smagt, J.J. van der, Nijman, IJ, Kloosterman, W.P., Haelst, M.M. van, Haaften, G. van, and Cuppen, E.
- Abstract
Item does not contain fulltext, Cantu syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals with Cantu syndrome examined. The ABCC9 protein is part of an ATP-dependent potassium (K(ATP)) channel that couples the metabolic state of a cell with its electrical activity. All mutations altered amino acids in or close to the transmembrane domains of ABCC9. Using electrophysiological measurements, we show that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. Moreover, similarities between the phenotype of individuals with Cantu syndrome and side effects from the K(ATP) channel agonist minoxidil indicate that the mutations in ABCC9 result in channel opening. Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantu syndrome.
- Published
- 2012
17. Systematic generation of in vivo G protein-coupled receptor mutants in the rat
- Author
-
Boxtel, R. van, Vroling, B., Toonen, P., Nijman, IJ, Roekel, H. van, Verheul, M., Baakman, C.A.B., Guryev, V., Vriend, G., Cuppen, E., Boxtel, R. van, Vroling, B., Toonen, P., Nijman, IJ, Roekel, H. van, Verheul, M., Baakman, C.A.B., Guryev, V., Vriend, G., and Cuppen, E.
- Abstract
Contains fulltext : 92398.pdf (publisher's version ) (Closed access)
- Published
- 2011
18. Systematic generation of in vivo G protein-coupled receptor mutants in the rat
- Author
-
Boxtel, R. van, Vroling, B., Toonen, P., Nijman, IJ, Roekel, H. van, Verheul, M., Baakman, C.A.B., Guryev, V., Vriend, G., Cuppen, E., Boxtel, R. van, Vroling, B., Toonen, P., Nijman, IJ, Roekel, H. van, Verheul, M., Baakman, C.A.B., Guryev, V., Vriend, G., and Cuppen, E.
- Abstract
Contains fulltext : 92398.pdf (publisher's version ) (Closed access)
- Published
- 2011
19. Systematic generation of in vivo G protein-coupled receptor mutants in the rat
- Author
-
Boxtel, R. van, Vroling, B., Toonen, P., Nijman, IJ, Roekel, H. van, Verheul, M., Baakman, C.A.B., Guryev, V., Vriend, G., Cuppen, E., Boxtel, R. van, Vroling, B., Toonen, P., Nijman, IJ, Roekel, H. van, Verheul, M., Baakman, C.A.B., Guryev, V., Vriend, G., and Cuppen, E.
- Abstract
Contains fulltext : 92398.pdf (publisher's version ) (Closed access)
- Published
- 2011
20. Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cells
- Author
-
Hatzis, P, Flier, LG van der, Driel, M.A. van, Guryev, V., Nielsen, F., Denissov, S., Nijman, IJ, Koster, J., Santo, E., Welboren, W., Versteeg, R., Cuppen, E., Wetering, M van de, Clevers, H., Stunnenberg, H.G., Hatzis, P, Flier, LG van der, Driel, M.A. van, Guryev, V., Nielsen, F., Denissov, S., Nijman, IJ, Koster, J., Santo, E., Welboren, W., Versteeg, R., Cuppen, E., Wetering, M van de, Clevers, H., and Stunnenberg, H.G.
- Abstract
Item does not contain fulltext
- Published
- 2008
21. Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cells
- Author
-
Hatzis, P, Flier, LG van der, Driel, M.A. van, Guryev, V., Nielsen, F., Denissov, S., Nijman, IJ, Koster, J., Santo, E., Welboren, W., Versteeg, R., Cuppen, E., Wetering, M van de, Clevers, H., Stunnenberg, H.G., Hatzis, P, Flier, LG van der, Driel, M.A. van, Guryev, V., Nielsen, F., Denissov, S., Nijman, IJ, Koster, J., Santo, E., Welboren, W., Versteeg, R., Cuppen, E., Wetering, M van de, Clevers, H., and Stunnenberg, H.G.
- Abstract
Item does not contain fulltext
- Published
- 2008
22. Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cells
- Author
-
Hatzis, P, Flier, LG van der, Driel, M.A. van, Guryev, V., Nielsen, F., Denissov, S., Nijman, IJ, Koster, J., Santo, E., Welboren, W., Versteeg, R., Cuppen, E., Wetering, M van de, Clevers, H., Stunnenberg, H.G., Hatzis, P, Flier, LG van der, Driel, M.A. van, Guryev, V., Nielsen, F., Denissov, S., Nijman, IJ, Koster, J., Santo, E., Welboren, W., Versteeg, R., Cuppen, E., Wetering, M van de, Clevers, H., and Stunnenberg, H.G.
- Abstract
Item does not contain fulltext
- Published
- 2008
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