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Kirschstein NRSA Individual Postdoctoral Fellowship","award":["DK122766"],"award-info":[{"award-number":["DK122766"]}]},{"DOI":"10.13039\/501100000191","name":"Kidney Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015452","name":"Canadian Society of Nephrology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015452","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32-DK007726"],"award-info":[{"award-number":["T32-DK007726"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32DK-007726"],"award-info":[{"award-number":["T32DK-007726"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008035","name":"Harvard Stem Cell Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008035","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Society of Nephrology Lipps Research Program 2018 Polycystic Kidney Disease Foundation Jared J. Grantham Research Fellowship"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["DK104309"],"award-info":[{"award-number":["DK104309"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["DK073462"],"award-info":[{"award-number":["DK073462"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>An underlying monogenic cause of early-onset chronic kidney disease (CKD) can be detected in \u223c20% of individuals. For many etiologies of CKD manifesting before 25\u2009years of age, &amp;gt;200 monogenic causative genes have been identified to date, leading to the elucidation of mechanisms of renal pathogenesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In 51 families with echogenic kidneys and CKD, we performed whole-exome sequencing to identify novel monogenic causes of CKD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We discovered a homozygous truncating mutation in the transcription factor gene transcription factor CP2-like 1 (TFCP2L1) in an Arabic patient of consanguineous descent. The patient developed CKD by the age of 2\u2009months and had episodes of severe hypochloremic, hyponatremic and hypokalemic alkalosis, seizures, developmental delay and hypotonia together with cataracts. We found that TFCP2L1\u00a0was localized throughout kidney development particularly in the distal nephron. Interestingly, TFCP2L1 induced the growth and development of renal tubules from rat mesenchymal cells. Conversely, the deletion of TFCP2L1\u00a0in mice was previously shown to lead to reduced expression of renal cell markers including ion transporters and cell identity proteins expressed in different segments of the distal nephron. TFCP2L1 localized to the nucleus in HEK293T cells only upon coexpression with its paralog upstream-binding protein 1 (UBP1). A TFCP2L1 mutant complementary DNA (cDNA) clone that represented the patient\u2019s mutation failed to form homo- and heterodimers with UBP1, an essential step for its transcriptional activity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Here, we identified a loss-of-function TFCP2L1 mutation as a potential novel cause of CKD in childhood accompanied by a salt-losing tubulopathy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfaa215","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T19:26:31Z","timestamp":1596569191000},"page":"237-246","source":"Crossref","is-referenced-by-count":6,"title":["Mutations in transcription factor CP2-like 1 may cause a novel syndrome with distal renal tubulopathy in humans"],"prefix":"10.1093","volume":"36","author":[{"given":"Verena","family":"Kl\u00e4mbt","sequence":"first","affiliation":[{"name":"Division of Nephrology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Werth","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C","family":"Onuchic-Whitford","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Renal Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Getwan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M","family":"Kitzler","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Buerger","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youying","family":"Mao","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2952-5030","authenticated-orcid":false,"given":"Konstantin","family":"Deutsch","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Mann","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar J","family":"Majmundar","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Berlin Institute for Medical Systems Biology, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany"},{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9 - Universitaetsmedizin Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai M","family":"Schmidt-Ott","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9 - Universitaetsmedizin Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Shalaby","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Center of Excellence and Pediatric Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif","family":"El Desoky","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Center of Excellence and Pediatric Department, Faculty of Medicine, King Abdulaziz University, 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