Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches

Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) c...
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Autor*in:	Verena Klämbt [verfasserIn] Youying Mao [verfasserIn] Ronen Schneider [verfasserIn] Florian Buerger [verfasserIn] Hanan Shamseldin [verfasserIn] Ana C. Onuchic-Whitford [verfasserIn] Konstantin Deutsch [verfasserIn] Thomas M. Kitzler [verfasserIn] Makiko Nakayama [verfasserIn] Amar J. Majmundar [verfasserIn] Nina Mann [verfasserIn] Hannah Hugo [verfasserIn] Eugen Widmeier [verfasserIn] Weizhen Tan [verfasserIn] Heidi L. Rehm [verfasserIn] Shrikant Mane [verfasserIn] Richard P. Lifton [verfasserIn] Fowzan S. Alkuraya [verfasserIn] Shirlee Shril [verfasserIn] Friedhelm Hildebrandt [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	pediatric nephrology proteinuria recessive disease whole-exome sequencing

Übergeordnetes Werk:	In: Kidney International Reports - Elsevier, 2016, 6(2021), 2, Seite 460-471
Übergeordnetes Werk:	volume:6 ; year:2021 ; number:2 ; pages:460-471

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.ekir.2020.11.013

Katalog-ID:	DOAJ007890931

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245	1	0	\|a Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches
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520			\|a Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS. Results: We first identified 63 known monogenic causes of NS in mice from public databases and scientific publications, and 12 of these genes overlapped with the 63 known human monogenic SRNS genes. Second, we used a set of 64 genes that are regulated by the transcription factor Wilms tumor 1 (WT1), which causes SRNS if mutated. Thirteen of these WT1-regulated genes overlapped with human or murine NS genes. Finally, we overlapped these lists of murine and WT1 candidate genes with our list of 120 candidate genes generated from WES in 1382 NS families, to identify novel candidate genes for monogenic human SRNS. Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. Conclusion: Thus, we identified 3 novel candidate genes for human SRNS using 3 independent, nonoverlapping hypotheses, and generated functional evidence for SYNPO as a novel potential monogenic cause of NS.
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700	0		\|a Ronen Schneider \|e verfasserin \|4 aut
700	0		\|a Florian Buerger \|e verfasserin \|4 aut
700	0		\|a Hanan Shamseldin \|e verfasserin \|4 aut
700	0		\|a Ana C. Onuchic-Whitford \|e verfasserin \|4 aut
700	0		\|a Konstantin Deutsch \|e verfasserin \|4 aut
700	0		\|a Thomas M. Kitzler \|e verfasserin \|4 aut
700	0		\|a Makiko Nakayama \|e verfasserin \|4 aut
700	0		\|a Amar J. Majmundar \|e verfasserin \|4 aut
700	0		\|a Nina Mann \|e verfasserin \|4 aut
700	0		\|a Hannah Hugo \|e verfasserin \|4 aut
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700	0		\|a Weizhen Tan \|e verfasserin \|4 aut
700	0		\|a Heidi L. Rehm \|e verfasserin \|4 aut
700	0		\|a Shrikant Mane \|e verfasserin \|4 aut
700	0		\|a Richard P. Lifton \|e verfasserin \|4 aut
700	0		\|a Fowzan S. Alkuraya \|e verfasserin \|4 aut
700	0		\|a Shirlee Shril \|e verfasserin \|4 aut
700	0		\|a Friedhelm Hildebrandt \|e verfasserin \|4 aut
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author_variant	v k vk y m ym r s rs f b fb h s hs a c o w acow k d kd t m k tmk m n mn a j m ajm n m nm h h hh e w ew w t wt h l r hlr s m sm r p l rpl f s a fsa s s ss f h fh
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allfields	10.1016/j.ekir.2020.11.013 doi (DE-627)DOAJ007890931 (DE-599)DOAJac1e1122125e4dcbb6b4e8d10596a17b DE-627 ger DE-627 rakwb eng RC870-923 Verena Klämbt verfasserin aut Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS. Results: We first identified 63 known monogenic causes of NS in mice from public databases and scientific publications, and 12 of these genes overlapped with the 63 known human monogenic SRNS genes. Second, we used a set of 64 genes that are regulated by the transcription factor Wilms tumor 1 (WT1), which causes SRNS if mutated. Thirteen of these WT1-regulated genes overlapped with human or murine NS genes. Finally, we overlapped these lists of murine and WT1 candidate genes with our list of 120 candidate genes generated from WES in 1382 NS families, to identify novel candidate genes for monogenic human SRNS. Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. Conclusion: Thus, we identified 3 novel candidate genes for human SRNS using 3 independent, nonoverlapping hypotheses, and generated functional evidence for SYNPO as a novel potential monogenic cause of NS. pediatric nephrology proteinuria recessive disease whole-exome sequencing Diseases of the genitourinary system. Urology Youying Mao verfasserin aut Ronen Schneider verfasserin aut Florian Buerger verfasserin aut Hanan Shamseldin verfasserin aut Ana C. Onuchic-Whitford verfasserin aut Konstantin Deutsch verfasserin aut Thomas M. Kitzler verfasserin aut Makiko Nakayama verfasserin aut Amar J. Majmundar verfasserin aut Nina Mann verfasserin aut Hannah Hugo verfasserin aut Eugen Widmeier verfasserin aut Weizhen Tan verfasserin aut Heidi L. Rehm verfasserin aut Shrikant Mane verfasserin aut Richard P. Lifton verfasserin aut Fowzan S. Alkuraya verfasserin aut Shirlee Shril verfasserin aut Friedhelm Hildebrandt verfasserin aut In Kidney International Reports Elsevier, 2016 6(2021), 2, Seite 460-471 (DE-627)881695580 (DE-600)2887223-X 24680249 nnns volume:6 year:2021 number:2 pages:460-471 https://doi.org/10.1016/j.ekir.2020.11.013 kostenfrei https://doaj.org/article/ac1e1122125e4dcbb6b4e8d10596a17b kostenfrei http://www.sciencedirect.com/science/article/pii/S2468024920317502 kostenfrei https://doaj.org/toc/2468-0249 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 6 2021 2 460-471
spelling	10.1016/j.ekir.2020.11.013 doi (DE-627)DOAJ007890931 (DE-599)DOAJac1e1122125e4dcbb6b4e8d10596a17b DE-627 ger DE-627 rakwb eng RC870-923 Verena Klämbt verfasserin aut Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS. Results: We first identified 63 known monogenic causes of NS in mice from public databases and scientific publications, and 12 of these genes overlapped with the 63 known human monogenic SRNS genes. Second, we used a set of 64 genes that are regulated by the transcription factor Wilms tumor 1 (WT1), which causes SRNS if mutated. Thirteen of these WT1-regulated genes overlapped with human or murine NS genes. Finally, we overlapped these lists of murine and WT1 candidate genes with our list of 120 candidate genes generated from WES in 1382 NS families, to identify novel candidate genes for monogenic human SRNS. Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. Conclusion: Thus, we identified 3 novel candidate genes for human SRNS using 3 independent, nonoverlapping hypotheses, and generated functional evidence for SYNPO as a novel potential monogenic cause of NS. pediatric nephrology proteinuria recessive disease whole-exome sequencing Diseases of the genitourinary system. Urology Youying Mao verfasserin aut Ronen Schneider verfasserin aut Florian Buerger verfasserin aut Hanan Shamseldin verfasserin aut Ana C. Onuchic-Whitford verfasserin aut Konstantin Deutsch verfasserin aut Thomas M. Kitzler verfasserin aut Makiko Nakayama verfasserin aut Amar J. Majmundar verfasserin aut Nina Mann verfasserin aut Hannah Hugo verfasserin aut Eugen Widmeier verfasserin aut Weizhen Tan verfasserin aut Heidi L. Rehm verfasserin aut Shrikant Mane verfasserin aut Richard P. Lifton verfasserin aut Fowzan S. Alkuraya verfasserin aut Shirlee Shril verfasserin aut Friedhelm Hildebrandt verfasserin aut In Kidney International Reports Elsevier, 2016 6(2021), 2, Seite 460-471 (DE-627)881695580 (DE-600)2887223-X 24680249 nnns volume:6 year:2021 number:2 pages:460-471 https://doi.org/10.1016/j.ekir.2020.11.013 kostenfrei https://doaj.org/article/ac1e1122125e4dcbb6b4e8d10596a17b kostenfrei http://www.sciencedirect.com/science/article/pii/S2468024920317502 kostenfrei https://doaj.org/toc/2468-0249 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 6 2021 2 460-471
allfields_unstemmed	10.1016/j.ekir.2020.11.013 doi (DE-627)DOAJ007890931 (DE-599)DOAJac1e1122125e4dcbb6b4e8d10596a17b DE-627 ger DE-627 rakwb eng RC870-923 Verena Klämbt verfasserin aut Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS. Results: We first identified 63 known monogenic causes of NS in mice from public databases and scientific publications, and 12 of these genes overlapped with the 63 known human monogenic SRNS genes. Second, we used a set of 64 genes that are regulated by the transcription factor Wilms tumor 1 (WT1), which causes SRNS if mutated. Thirteen of these WT1-regulated genes overlapped with human or murine NS genes. Finally, we overlapped these lists of murine and WT1 candidate genes with our list of 120 candidate genes generated from WES in 1382 NS families, to identify novel candidate genes for monogenic human SRNS. Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. Conclusion: Thus, we identified 3 novel candidate genes for human SRNS using 3 independent, nonoverlapping hypotheses, and generated functional evidence for SYNPO as a novel potential monogenic cause of NS. pediatric nephrology proteinuria recessive disease whole-exome sequencing Diseases of the genitourinary system. Urology Youying Mao verfasserin aut Ronen Schneider verfasserin aut Florian Buerger verfasserin aut Hanan Shamseldin verfasserin aut Ana C. Onuchic-Whitford verfasserin aut Konstantin Deutsch verfasserin aut Thomas M. Kitzler verfasserin aut Makiko Nakayama verfasserin aut Amar J. Majmundar verfasserin aut Nina Mann verfasserin aut Hannah Hugo verfasserin aut Eugen Widmeier verfasserin aut Weizhen Tan verfasserin aut Heidi L. Rehm verfasserin aut Shrikant Mane verfasserin aut Richard P. Lifton verfasserin aut Fowzan S. Alkuraya verfasserin aut Shirlee Shril verfasserin aut Friedhelm Hildebrandt verfasserin aut In Kidney International Reports Elsevier, 2016 6(2021), 2, Seite 460-471 (DE-627)881695580 (DE-600)2887223-X 24680249 nnns volume:6 year:2021 number:2 pages:460-471 https://doi.org/10.1016/j.ekir.2020.11.013 kostenfrei https://doaj.org/article/ac1e1122125e4dcbb6b4e8d10596a17b kostenfrei http://www.sciencedirect.com/science/article/pii/S2468024920317502 kostenfrei https://doaj.org/toc/2468-0249 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 6 2021 2 460-471
allfieldsGer	10.1016/j.ekir.2020.11.013 doi (DE-627)DOAJ007890931 (DE-599)DOAJac1e1122125e4dcbb6b4e8d10596a17b DE-627 ger DE-627 rakwb eng RC870-923 Verena Klämbt verfasserin aut Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS. Results: We first identified 63 known monogenic causes of NS in mice from public databases and scientific publications, and 12 of these genes overlapped with the 63 known human monogenic SRNS genes. Second, we used a set of 64 genes that are regulated by the transcription factor Wilms tumor 1 (WT1), which causes SRNS if mutated. Thirteen of these WT1-regulated genes overlapped with human or murine NS genes. Finally, we overlapped these lists of murine and WT1 candidate genes with our list of 120 candidate genes generated from WES in 1382 NS families, to identify novel candidate genes for monogenic human SRNS. Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. Conclusion: Thus, we identified 3 novel candidate genes for human SRNS using 3 independent, nonoverlapping hypotheses, and generated functional evidence for SYNPO as a novel potential monogenic cause of NS. pediatric nephrology proteinuria recessive disease whole-exome sequencing Diseases of the genitourinary system. Urology Youying Mao verfasserin aut Ronen Schneider verfasserin aut Florian Buerger verfasserin aut Hanan Shamseldin verfasserin aut Ana C. Onuchic-Whitford verfasserin aut Konstantin Deutsch verfasserin aut Thomas M. Kitzler verfasserin aut Makiko Nakayama verfasserin aut Amar J. Majmundar verfasserin aut Nina Mann verfasserin aut Hannah Hugo verfasserin aut Eugen Widmeier verfasserin aut Weizhen Tan verfasserin aut Heidi L. Rehm verfasserin aut Shrikant Mane verfasserin aut Richard P. Lifton verfasserin aut Fowzan S. Alkuraya verfasserin aut Shirlee Shril verfasserin aut Friedhelm Hildebrandt verfasserin aut In Kidney International Reports Elsevier, 2016 6(2021), 2, Seite 460-471 (DE-627)881695580 (DE-600)2887223-X 24680249 nnns volume:6 year:2021 number:2 pages:460-471 https://doi.org/10.1016/j.ekir.2020.11.013 kostenfrei https://doaj.org/article/ac1e1122125e4dcbb6b4e8d10596a17b kostenfrei http://www.sciencedirect.com/science/article/pii/S2468024920317502 kostenfrei https://doaj.org/toc/2468-0249 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 6 2021 2 460-471
allfieldsSound	10.1016/j.ekir.2020.11.013 doi (DE-627)DOAJ007890931 (DE-599)DOAJac1e1122125e4dcbb6b4e8d10596a17b DE-627 ger DE-627 rakwb eng RC870-923 Verena Klämbt verfasserin aut Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS. Results: We first identified 63 known monogenic causes of NS in mice from public databases and scientific publications, and 12 of these genes overlapped with the 63 known human monogenic SRNS genes. Second, we used a set of 64 genes that are regulated by the transcription factor Wilms tumor 1 (WT1), which causes SRNS if mutated. Thirteen of these WT1-regulated genes overlapped with human or murine NS genes. Finally, we overlapped these lists of murine and WT1 candidate genes with our list of 120 candidate genes generated from WES in 1382 NS families, to identify novel candidate genes for monogenic human SRNS. Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. Conclusion: Thus, we identified 3 novel candidate genes for human SRNS using 3 independent, nonoverlapping hypotheses, and generated functional evidence for SYNPO as a novel potential monogenic cause of NS. pediatric nephrology proteinuria recessive disease whole-exome sequencing Diseases of the genitourinary system. Urology Youying Mao verfasserin aut Ronen Schneider verfasserin aut Florian Buerger verfasserin aut Hanan Shamseldin verfasserin aut Ana C. Onuchic-Whitford verfasserin aut Konstantin Deutsch verfasserin aut Thomas M. Kitzler verfasserin aut Makiko Nakayama verfasserin aut Amar J. Majmundar verfasserin aut Nina Mann verfasserin aut Hannah Hugo verfasserin aut Eugen Widmeier verfasserin aut Weizhen Tan verfasserin aut Heidi L. Rehm verfasserin aut Shrikant Mane verfasserin aut Richard P. Lifton verfasserin aut Fowzan S. Alkuraya verfasserin aut Shirlee Shril verfasserin aut Friedhelm Hildebrandt verfasserin aut In Kidney International Reports Elsevier, 2016 6(2021), 2, Seite 460-471 (DE-627)881695580 (DE-600)2887223-X 24680249 nnns volume:6 year:2021 number:2 pages:460-471 https://doi.org/10.1016/j.ekir.2020.11.013 kostenfrei https://doaj.org/article/ac1e1122125e4dcbb6b4e8d10596a17b kostenfrei http://www.sciencedirect.com/science/article/pii/S2468024920317502 kostenfrei https://doaj.org/toc/2468-0249 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 6 2021 2 460-471
language	English
source	In Kidney International Reports 6(2021), 2, Seite 460-471 volume:6 year:2021 number:2 pages:460-471
sourceStr	In Kidney International Reports 6(2021), 2, Seite 460-471 volume:6 year:2021 number:2 pages:460-471
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	pediatric nephrology proteinuria recessive disease whole-exome sequencing Diseases of the genitourinary system. Urology
isfreeaccess_bool	true
container_title	Kidney International Reports
authorswithroles_txt_mv	Verena Klämbt @@aut@@ Youying Mao @@aut@@ Ronen Schneider @@aut@@ Florian Buerger @@aut@@ Hanan Shamseldin @@aut@@ Ana C. Onuchic-Whitford @@aut@@ Konstantin Deutsch @@aut@@ Thomas M. Kitzler @@aut@@ Makiko Nakayama @@aut@@ Amar J. Majmundar @@aut@@ Nina Mann @@aut@@ Hannah Hugo @@aut@@ Eugen Widmeier @@aut@@ Weizhen Tan @@aut@@ Heidi L. Rehm @@aut@@ Shrikant Mane @@aut@@ Richard P. Lifton @@aut@@ Fowzan S. Alkuraya @@aut@@ Shirlee Shril @@aut@@ Friedhelm Hildebrandt @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	881695580
id	DOAJ007890931
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ007890931</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230501184020.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230225s2021 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ekir.2020.11.013</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ007890931</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJac1e1122125e4dcbb6b4e8d10596a17b</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC870-923</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Verena Klämbt</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. 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Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. 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callnumber-first	R - Medicine
author	Verena Klämbt
spellingShingle	Verena Klämbt misc RC870-923 misc pediatric nephrology misc proteinuria misc recessive disease misc whole-exome sequencing misc Diseases of the genitourinary system. Urology Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches
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topic_title	RC870-923 Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches pediatric nephrology proteinuria recessive disease whole-exome sequencing
topic	misc RC870-923 misc pediatric nephrology misc proteinuria misc recessive disease misc whole-exome sequencing misc Diseases of the genitourinary system. Urology
topic_unstemmed	misc RC870-923 misc pediatric nephrology misc proteinuria misc recessive disease misc whole-exome sequencing misc Diseases of the genitourinary system. Urology
topic_browse	misc RC870-923 misc pediatric nephrology misc proteinuria misc recessive disease misc whole-exome sequencing misc Diseases of the genitourinary system. Urology
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title	Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches
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title_full	Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches
author_sort	Verena Klämbt
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author_browse	Verena Klämbt Youying Mao Ronen Schneider Florian Buerger Hanan Shamseldin Ana C. Onuchic-Whitford Konstantin Deutsch Thomas M. Kitzler Makiko Nakayama Amar J. Majmundar Nina Mann Hannah Hugo Eugen Widmeier Weizhen Tan Heidi L. Rehm Shrikant Mane Richard P. Lifton Fowzan S. Alkuraya Shirlee Shril Friedhelm Hildebrandt
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doi_str_mv	10.1016/j.ekir.2020.11.013
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title_sort	generation of monogenic candidate genes for human nephrotic syndrome using 3 independent approaches
callnumber	RC870-923
title_auth	Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches
abstract	Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS. Results: We first identified 63 known monogenic causes of NS in mice from public databases and scientific publications, and 12 of these genes overlapped with the 63 known human monogenic SRNS genes. Second, we used a set of 64 genes that are regulated by the transcription factor Wilms tumor 1 (WT1), which causes SRNS if mutated. Thirteen of these WT1-regulated genes overlapped with human or murine NS genes. Finally, we overlapped these lists of murine and WT1 candidate genes with our list of 120 candidate genes generated from WES in 1382 NS families, to identify novel candidate genes for monogenic human SRNS. Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. Conclusion: Thus, we identified 3 novel candidate genes for human SRNS using 3 independent, nonoverlapping hypotheses, and generated functional evidence for SYNPO as a novel potential monogenic cause of NS.
abstractGer	Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS. Results: We first identified 63 known monogenic causes of NS in mice from public databases and scientific publications, and 12 of these genes overlapped with the 63 known human monogenic SRNS genes. Second, we used a set of 64 genes that are regulated by the transcription factor Wilms tumor 1 (WT1), which causes SRNS if mutated. Thirteen of these WT1-regulated genes overlapped with human or murine NS genes. Finally, we overlapped these lists of murine and WT1 candidate genes with our list of 120 candidate genes generated from WES in 1382 NS families, to identify novel candidate genes for monogenic human SRNS. Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. Conclusion: Thus, we identified 3 novel candidate genes for human SRNS using 3 independent, nonoverlapping hypotheses, and generated functional evidence for SYNPO as a novel potential monogenic cause of NS.
abstract_unstemmed	Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS. Results: We first identified 63 known monogenic causes of NS in mice from public databases and scientific publications, and 12 of these genes overlapped with the 63 known human monogenic SRNS genes. Second, we used a set of 64 genes that are regulated by the transcription factor Wilms tumor 1 (WT1), which causes SRNS if mutated. Thirteen of these WT1-regulated genes overlapped with human or murine NS genes. Finally, we overlapped these lists of murine and WT1 candidate genes with our list of 120 candidate genes generated from WES in 1382 NS families, to identify novel candidate genes for monogenic human SRNS. Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. Conclusion: Thus, we identified 3 novel candidate genes for human SRNS using 3 independent, nonoverlapping hypotheses, and generated functional evidence for SYNPO as a novel potential monogenic cause of NS.
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title_short	Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches
url	https://doi.org/10.1016/j.ekir.2020.11.013 https://doaj.org/article/ac1e1122125e4dcbb6b4e8d10596a17b http://www.sciencedirect.com/science/article/pii/S2468024920317502 https://doaj.org/toc/2468-0249
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author2	Youying Mao Ronen Schneider Florian Buerger Hanan Shamseldin Ana C. Onuchic-Whitford Konstantin Deutsch Thomas M. Kitzler Makiko Nakayama Amar J. Majmundar Nina Mann Hannah Hugo Eugen Widmeier Weizhen Tan Heidi L. Rehm Shrikant Mane Richard P. Lifton Fowzan S. Alkuraya Shirlee Shril Friedhelm Hildebrandt
author2Str	Youying Mao Ronen Schneider Florian Buerger Hanan Shamseldin Ana C. Onuchic-Whitford Konstantin Deutsch Thomas M. Kitzler Makiko Nakayama Amar J. Majmundar Nina Mann Hannah Hugo Eugen Widmeier Weizhen Tan Heidi L. Rehm Shrikant Mane Richard P. Lifton Fowzan S. Alkuraya Shirlee Shril Friedhelm Hildebrandt
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doi_str	10.1016/j.ekir.2020.11.013
callnumber-a	RC870-923
up_date	2024-07-03T14:43:59.471Z
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Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways. Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS. Results: We first identified 63 known monogenic causes of NS in mice from public databases and scientific publications, and 12 of these genes overlapped with the 63 known human monogenic SRNS genes. Second, we used a set of 64 genes that are regulated by the transcription factor Wilms tumor 1 (WT1), which causes SRNS if mutated. Thirteen of these WT1-regulated genes overlapped with human or murine NS genes. Finally, we overlapped these lists of murine and WT1 candidate genes with our list of 120 candidate genes generated from WES in 1382 NS families, to identify novel candidate genes for monogenic human SRNS. Using this approach, we identified 7 overlapping genes, of which 3 genes were shared by all datasets, including SYNPO. We show that loss-of-function of SYNPO leads to decreased CDC42 activity and reduced podocyte migration rate, both of which are rescued by overexpression of wild-type complementary DNA (cDNA), but not by cDNA representing the patient mutation. 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Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches

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