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19 results on '"Oud, Machteld M"'

1. NANS-CDG:Delineation of the Genetic, Biochemical, and Clinical Spectrum

Author

den Hollander, Bibiche, Rasing, Anne, Post, Merel A., Klein, Willemijn M., Oud, Machteld M., Brands, Marion M., de Boer, Lonneke, Engelke, Udo F.H., van Essen, Peter, Fuchs, Sabine A., Haaxma, Charlotte A., Jensson, Brynjar O., Kluijtmans, Leo A.J., Lengyel, Anna, Lichtenbelt, Klaske D., Østergaard, Elsebet, Peters, Gera, Salvarinova, Ramona, Simon, Marleen E.H., Stefansson, Kari, Thorarensen, Ólafur, Ulmen, Ulrike, Coene, Karlien L.M., Willemsen, Michèl A., Lefeber, Dirk J., Karnebeek, Clara D.M.van, den Hollander, Bibiche, Rasing, Anne, Post, Merel A., Klein, Willemijn M., Oud, Machteld M., Brands, Marion M., de Boer, Lonneke, Engelke, Udo F.H., van Essen, Peter, Fuchs, Sabine A., Haaxma, Charlotte A., Jensson, Brynjar O., Kluijtmans, Leo A.J., Lengyel, Anna, Lichtenbelt, Klaske D., Østergaard, Elsebet, Peters, Gera, Salvarinova, Ramona, Simon, Marleen E.H., Stefansson, Kari, Thorarensen, Ólafur, Ulmen, Ulrike, Coene, Karlien L.M., Willemsen, Michèl A., Lefeber, Dirk J., and Karnebeek, Clara D.M.van

Abstract

Background: NANS-CDG is a recently described congenital disorder of glycosylation caused by biallelic genetic variants in NANS, encoding an essential enzyme in de novo sialic acid synthesis. Sialic acid at the end of glycoconjugates plays a key role in biological processes such as brain and skeletal development. Here, we present an observational cohort study to delineate the genetic, biochemical, and clinical phenotype and assess possible correlations. Methods: Medical and laboratory records were reviewed with retrospective extraction and analysis of genetic, biochemical, and clinical data (2016–2020). Results: Nine NANS-CDG patients (nine families, six countries) referred to the Radboudumc CDG Center of Expertise were included. Phenotyping confirmed the hallmark features including intellectual developmental disorder (IDD) (n = 9/9; 100%), facial dysmorphisms (n = 9/9; 100%), neurologic impairment (n = 9/9; 100%), short stature (n = 8/9; 89%), skeletal dysplasia (n = 8/9; 89%), and short limbs (n = 8/9; 89%). Newly identified features include ophthalmological abnormalities (n = 6/9; 67%), an abnormal septum pellucidum (n = 6/9; 67%), (progressive) cerebral atrophy and ventricular dilatation (n = 5/9; 56%), gastrointestinal dysfunction (n = 5/9; 56%), thrombocytopenia (n = 5/9; 56%), and hypo–low-density lipoprotein cholesterol (n = 4/9; 44%). Biochemically, elevated urinary excretion of N-acetylmannosamine (ManNAc) is pathognomonic, the concentrations of which show a significant correlation with clinical severity. Genotypically, eight novel NANS variants were identified. Three severely affected patients harbored identical compound heterozygous pathogenic variants, one of whom was initiated on experimental prenatal and postnatal treatment with oral sialic acid. This patient showed markedly better psychomotor development than the other two genotypically identical males. Conclusions: ManNAc screening should be considered in all patients with IDD, short stature with

Published
2021

2. NANS-CDG:Delineation of the Genetic, Biochemical, and Clinical Spectrum

Author

den Hollander, Bibiche, Rasing, Anne, Post, Merel A., Klein, Willemijn M., Oud, Machteld M., Brands, Marion M., de Boer, Lonneke, Engelke, Udo F.H., van Essen, Peter, Fuchs, Sabine A., Haaxma, Charlotte A., Jensson, Brynjar O., Kluijtmans, Leo A.J., Lengyel, Anna, Lichtenbelt, Klaske D., Østergaard, Elsebet, Peters, Gera, Salvarinova, Ramona, Simon, Marleen E.H., Stefansson, Kari, Thorarensen, Ólafur, Ulmen, Ulrike, Coene, Karlien L.M., Willemsen, Michèl A., Lefeber, Dirk J., Karnebeek, Clara D.M.van, den Hollander, Bibiche, Rasing, Anne, Post, Merel A., Klein, Willemijn M., Oud, Machteld M., Brands, Marion M., de Boer, Lonneke, Engelke, Udo F.H., van Essen, Peter, Fuchs, Sabine A., Haaxma, Charlotte A., Jensson, Brynjar O., Kluijtmans, Leo A.J., Lengyel, Anna, Lichtenbelt, Klaske D., Østergaard, Elsebet, Peters, Gera, Salvarinova, Ramona, Simon, Marleen E.H., Stefansson, Kari, Thorarensen, Ólafur, Ulmen, Ulrike, Coene, Karlien L.M., Willemsen, Michèl A., Lefeber, Dirk J., and Karnebeek, Clara D.M.van

Abstract

Background: NANS-CDG is a recently described congenital disorder of glycosylation caused by biallelic genetic variants in NANS, encoding an essential enzyme in de novo sialic acid synthesis. Sialic acid at the end of glycoconjugates plays a key role in biological processes such as brain and skeletal development. Here, we present an observational cohort study to delineate the genetic, biochemical, and clinical phenotype and assess possible correlations. Methods: Medical and laboratory records were reviewed with retrospective extraction and analysis of genetic, biochemical, and clinical data (2016–2020). Results: Nine NANS-CDG patients (nine families, six countries) referred to the Radboudumc CDG Center of Expertise were included. Phenotyping confirmed the hallmark features including intellectual developmental disorder (IDD) (n = 9/9; 100%), facial dysmorphisms (n = 9/9; 100%), neurologic impairment (n = 9/9; 100%), short stature (n = 8/9; 89%), skeletal dysplasia (n = 8/9; 89%), and short limbs (n = 8/9; 89%). Newly identified features include ophthalmological abnormalities (n = 6/9; 67%), an abnormal septum pellucidum (n = 6/9; 67%), (progressive) cerebral atrophy and ventricular dilatation (n = 5/9; 56%), gastrointestinal dysfunction (n = 5/9; 56%), thrombocytopenia (n = 5/9; 56%), and hypo–low-density lipoprotein cholesterol (n = 4/9; 44%). Biochemically, elevated urinary excretion of N-acetylmannosamine (ManNAc) is pathognomonic, the concentrations of which show a significant correlation with clinical severity. Genotypically, eight novel NANS variants were identified. Three severely affected patients harbored identical compound heterozygous pathogenic variants, one of whom was initiated on experimental prenatal and postnatal treatment with oral sialic acid. This patient showed markedly better psychomotor development than the other two genotypically identical males. Conclusions: ManNAc screening should be considered in all patients with IDD, short stature with

Published
2021

3. NANS-CDG: Delineation of the Genetic, Biochemical, and Clinical Spectrum

Author

Metabole ziekten patientenzorg, Child Health, Regenerative Medicine and Stem Cells, Genetica Klinische Genetica, den Hollander, Bibiche, Rasing, Anne, Post, Merel A, Klein, Willemijn M, Oud, Machteld M, Brands, Marion M, de Boer, Lonneke, Engelke, Udo F H, van Essen, Peter, Fuchs, Sabine A, Haaxma, Charlotte A, Jensson, Brynjar O, Kluijtmans, Leo A J, Lengyel, Anna, Lichtenbelt, Klaske D, Østergaard, Elsebet, Peters, Gera, Salvarinova, Ramona, Simon, Marleen E H, Stefansson, Kari, Thorarensen, Ólafur, Ulmen, Ulrike, Coene, Karlien L M, Willemsen, Michèl A, Lefeber, Dirk J, van Karnebeek, Clara D M, Metabole ziekten patientenzorg, Child Health, Regenerative Medicine and Stem Cells, Genetica Klinische Genetica, den Hollander, Bibiche, Rasing, Anne, Post, Merel A, Klein, Willemijn M, Oud, Machteld M, Brands, Marion M, de Boer, Lonneke, Engelke, Udo F H, van Essen, Peter, Fuchs, Sabine A, Haaxma, Charlotte A, Jensson, Brynjar O, Kluijtmans, Leo A J, Lengyel, Anna, Lichtenbelt, Klaske D, Østergaard, Elsebet, Peters, Gera, Salvarinova, Ramona, Simon, Marleen E H, Stefansson, Kari, Thorarensen, Ólafur, Ulmen, Ulrike, Coene, Karlien L M, Willemsen, Michèl A, Lefeber, Dirk J, and van Karnebeek, Clara D M

Published
2021

4. CiliaCarta: An integrated and validated compendium of ciliary genes

Author

van Dam, T.J.P., Kennedy, Julie E., van der Lee, Robin, De Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard, Lambacher, Nils J., Li, Chunmei, Jensen, Victor L, Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, Van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., Van Wijk, Erwin, Kepes, François, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh Minh T., Letteboer, Stef J.F., Oud, Machteld M., Van Beersum, Sylvia E.C., Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, Huynen, Martijn H., van Dam, T.J.P., Kennedy, Julie E., van der Lee, Robin, De Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard, Lambacher, Nils J., Li, Chunmei, Jensen, Victor L, Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, Van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., Van Wijk, Erwin, Kepes, François, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh Minh T., Letteboer, Stef J.F., Oud, Machteld M., Van Beersum, Sylvia E.C., Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, and Huynen, Martijn H.

Abstract

The cilium is an essential organelle at the surface of most mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We found experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins. In addition, we show that OSCP1, which has previously been implicated in two distinct non-ciliary functions, causes a cilium dysfunction phenotype when depleted in zebrafish. The candidate list forms the basis of CiliaCarta, a comprehensive ciliary compendium covering 836 genes. The resource can be used to objectively prioritize candidate genes in whole exome or genome sequencing of ciliopathy patients and can be accessed at http://bioinformatics.bio.uu.nl/john/syscilia/ciliacarta/.

Published
2019

5. CiliaCarta: An integrated and validated compendium of ciliary genes

Author

van Dam, Teunis J. P., Kennedy, Julie, van der Lee, Robin, de Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard W., Lambacher, Nils J., Li, Chunmei, Jensen, Victor L., Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., van Wijk, Erwin, Kepes, Francois, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh-Minh T., Letteboer, Stef J. F., Oud, Machteld M., van Beersum, Sylvia E. C., Schmidts, Miriam, Beales, Philip L., Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, Huynen, Martijn A., van Dam, Teunis J. P., Kennedy, Julie, van der Lee, Robin, de Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard W., Lambacher, Nils J., Li, Chunmei, Jensen, Victor L., Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., van Wijk, Erwin, Kepes, Francois, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh-Minh T., Letteboer, Stef J. F., Oud, Machteld M., van Beersum, Sylvia E. C., Schmidts, Miriam, Beales, Philip L., Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, and Huynen, Martijn A.

Abstract

The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse, zebrafish and nematode) and techniques. For example, we show that OSCP1, which has previously been implicated in two distinct non-ciliary processes, causes ciliogenic and ciliopathy-associated tissue phenotypes when depleted in zebrafish. The candidate list forms the basis of CiliaCarta, a comprehensive ciliary compendium covering 956 genes. The resource can be used to objectively prioritize candidate genes in whole exome or genome sequencing of ciliopathy patients and can be accessed at http://bioinformatics.bio.uu.nl/john/syscilia/ciliacarta/.

Published
2019

6. CiliaCarta: An integrated and validated compendium of ciliary genes

Author

Sub Bioinformatics, Theoretical Biology and Bioinformatics, van Dam, T.J.P., Kennedy, Julie E., van der Lee, Robin, De Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard, Lambacher, Nils J., Li, Chunmei, Jensen, Victor L, Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, Van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., Van Wijk, Erwin, Kepes, François, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh Minh T., Letteboer, Stef J.F., Oud, Machteld M., Van Beersum, Sylvia E.C., Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, Huynen, Martijn H., Sub Bioinformatics, Theoretical Biology and Bioinformatics, van Dam, T.J.P., Kennedy, Julie E., van der Lee, Robin, De Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard, Lambacher, Nils J., Li, Chunmei, Jensen, Victor L, Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, Van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., Van Wijk, Erwin, Kepes, François, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh Minh T., Letteboer, Stef J.F., Oud, Machteld M., Van Beersum, Sylvia E.C., Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, and Huynen, Martijn H.

Published
2019

7. CiliaCarta: An integrated and validated compendium of ciliary genes

Author

Sub Bioinformatics, Theoretical Biology and Bioinformatics, van Dam, T.J.P., Kennedy, Julie E., van der Lee, Robin, De Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard, Lambacher, Nils J., Li, Chunmei, Jensen, Victor L, Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, Van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., Van Wijk, Erwin, Kepes, François, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh Minh T., Letteboer, Stef J.F., Oud, Machteld M., Van Beersum, Sylvia E.C., Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, Huynen, Martijn H., Sub Bioinformatics, Theoretical Biology and Bioinformatics, van Dam, T.J.P., Kennedy, Julie E., van der Lee, Robin, De Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard, Lambacher, Nils J., Li, Chunmei, Jensen, Victor L, Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, Van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., Van Wijk, Erwin, Kepes, François, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh Minh T., Letteboer, Stef J.F., Oud, Machteld M., Van Beersum, Sylvia E.C., Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, and Huynen, Martijn H.

Published
2019

8. CiliaCarta: An integrated and validated compendium of ciliary genes

Author

Sub Bioinformatics, Theoretical Biology and Bioinformatics, van Dam, T.J.P., Kennedy, Julie E., van der Lee, Robin, De Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard, Lambacher, Nils J., Li, Chunmei, Jensen, Victor L, Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, Van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., Van Wijk, Erwin, Kepes, François, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh Minh T., Letteboer, Stef J.F., Oud, Machteld M., Van Beersum, Sylvia E.C., Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, Huynen, Martijn H., Sub Bioinformatics, Theoretical Biology and Bioinformatics, van Dam, T.J.P., Kennedy, Julie E., van der Lee, Robin, De Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard, Lambacher, Nils J., Li, Chunmei, Jensen, Victor L, Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, Van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., Van Wijk, Erwin, Kepes, François, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh Minh T., Letteboer, Stef J.F., Oud, Machteld M., Van Beersum, Sylvia E.C., Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, and Huynen, Martijn H.

Published
2019

9. CiliaCarta: An integrated and validated compendium of ciliary genes

Author

van Dam, Teunis J. P., Kennedy, Julie, van der Lee, Robin, de Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard W., Lambacher, Nils J., Li, Chunmei, Jensen, Victor L., Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., van Wijk, Erwin, Kepes, Francois, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh-Minh T., Letteboer, Stef J. F., Oud, Machteld M., van Beersum, Sylvia E. C., Schmidts, Miriam, Beales, Philip L., Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, Huynen, Martijn A., van Dam, Teunis J. P., Kennedy, Julie, van der Lee, Robin, de Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard W., Lambacher, Nils J., Li, Chunmei, Jensen, Victor L., Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., Franco, Brunella, Mans, Dorus A., van Wijk, Erwin, Kepes, Francois, Slaats, Gisela G., Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh-Minh T., Letteboer, Stef J. F., Oud, Machteld M., van Beersum, Sylvia E. C., Schmidts, Miriam, Beales, Philip L., Lu, Qianhao, Giles, Rachel H., Szklarczyk, Radek, Russell, Robert B., Gibson, Toby J., Johnson, Colin A., Blacque, Oliver E., Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, and Huynen, Martijn A.

Abstract

The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse, zebrafish and nematode) and techniques. For example, we show that OSCP1, which has previously been implicated in two distinct non-ciliary processes, causes ciliogenic and ciliopathy-associated tissue phenotypes when depleted in zebrafish. The candidate list forms the basis of CiliaCarta, a comprehensive ciliary compendium covering 956 genes. The resource can be used to objectively prioritize candidate genes in whole exome or genome sequencing of ciliopathy patients and can be accessed at http://bioinformatics.bio.uu.nl/john/syscilia/ciliacarta/.

Published
2019

10. CiliaCarta: An integrated and validated compendium of ciliary genes

Author

Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, Circulatory Health, van Dam, Teunis J P, Kennedy, Julie, van der Lee, Robin, de Vrieze, Erik, Wunderlich, Kirsten A, Rix, Suzanne, Dougherty, Gerard W, Lambacher, Nils J, Li, Chunmei, Jensen, Victor L, Leroux, Michel R, Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F, Franco, Brunella, Mans, Dorus A, van Wijk, Erwin, Képès, François, Slaats, Gisela G, Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh-Minh T, Letteboer, Stef J F, Oud, Machteld M, van Beersum, Sylvia E C, Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H, Szklarczyk, Radek, Russell, Robert B, Gibson, Toby J, Johnson, Colin A, Blacque, Oliver E, Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, Huynen, Martijn A, Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, Circulatory Health, van Dam, Teunis J P, Kennedy, Julie, van der Lee, Robin, de Vrieze, Erik, Wunderlich, Kirsten A, Rix, Suzanne, Dougherty, Gerard W, Lambacher, Nils J, Li, Chunmei, Jensen, Victor L, Leroux, Michel R, Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F, Franco, Brunella, Mans, Dorus A, van Wijk, Erwin, Képès, François, Slaats, Gisela G, Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantinos, Ueffing, Marius, Nguyen, Thanh-Minh T, Letteboer, Stef J F, Oud, Machteld M, van Beersum, Sylvia E C, Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H, Szklarczyk, Radek, Russell, Robert B, Gibson, Toby J, Johnson, Colin A, Blacque, Oliver E, Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, and Huynen, Martijn A

Published
2019

14. The KOUNCIL Consortium: From Genetic Defects to Therapeutic Development for Nephronophthisis

Author

Genetica Sectie Research, Child Health, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, Nefrologie, Genetica, Renkema, Kirsten Y, Giles, Rachel H, Lilien, Marc R, Beales, Philip L, Roepman, Ronald, Oud, Machteld M, Arts, Heleen H, Knoers, Nine V A M, Genetica Sectie Research, Child Health, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, Nefrologie, Genetica, Renkema, Kirsten Y, Giles, Rachel H, Lilien, Marc R, Beales, Philip L, Roepman, Ronald, Oud, Machteld M, Arts, Heleen H, and Knoers, Nine V A M

Published
2018

15. De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia

Author

Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, van Haelst, Mieke M, Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, and van Haelst, Mieke M

Published
2016

16. De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia

Author

Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, van Haelst, Mieke M, Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, and van Haelst, Mieke M

Published
2016

17. De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia

Author

Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, van Haelst, Mieke M, Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, and van Haelst, Mieke M

Published
2016

18. De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia

Author

Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Child Health, Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, Genetica Groep Van Tintelen, Cancer, Genetica Medische Informatica, Circulatory Health, Genetica, Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, van Haelst, Mieke M, Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Child Health, Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, Genetica Groep Van Tintelen, Cancer, Genetica Medische Informatica, Circulatory Health, Genetica, Stokman, Marijn F, Oud, Machteld M, van Binsbergen, Ellen, Slaats, Gisela G, Nicolaou, Nayia, Renkema, Kirsten Y, Nijman, Isaac J, Roepman, Ronald, Giles, Rachel H, Arts, Heleen H, Knoers, Nine V A M, and van Haelst, Mieke M

Published
2016

19. Mutations in the gene encoding IFT dynein complex component WDR34 cause Jeune asphyxiating thoracic dystrophy.

Author

Schmidts, Miriam, Schmidts, Miriam, Vodopiutz, Julia, Christou-Savina, Sonia, Cortés, Claudio R, McInerney-Leo, Aideen M, Emes, Richard D, Arts, Heleen H, Tüysüz, Beyhan, D'Silva, Jason, Leo, Paul J, Giles, Tom C, Oud, Machteld M, Harris, Jessica A, Koopmans, Marije, Marshall, Mhairi, Elçioglu, Nursel, Kuechler, Alma, Bockenhauer, Detlef, Moore, Anthony T, Wilson, Louise C, Janecke, Andreas R, Hurles, Matthew E, Emmet, Warren, Gardiner, Brooke, Streubel, Berthold, Dopita, Belinda, Zankl, Andreas, Kayserili, Hülya, Scambler, Peter J, Brown, Matthew A, Beales, Philip L, Wicking, Carol, UK10K, Duncan, Emma L, Mitchison, Hannah M, Schmidts, Miriam, Schmidts, Miriam, Vodopiutz, Julia, Christou-Savina, Sonia, Cortés, Claudio R, McInerney-Leo, Aideen M, Emes, Richard D, Arts, Heleen H, Tüysüz, Beyhan, D'Silva, Jason, Leo, Paul J, Giles, Tom C, Oud, Machteld M, Harris, Jessica A, Koopmans, Marije, Marshall, Mhairi, Elçioglu, Nursel, Kuechler, Alma, Bockenhauer, Detlef, Moore, Anthony T, Wilson, Louise C, Janecke, Andreas R, Hurles, Matthew E, Emmet, Warren, Gardiner, Brooke, Streubel, Berthold, Dopita, Belinda, Zankl, Andreas, Kayserili, Hülya, Scambler, Peter J, Brown, Matthew A, Beales, Philip L, Wicking, Carol, UK10K, Duncan, Emma L, and Mitchison, Hannah M

Abstract

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Published
2013

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