@article {401,
	title = {A Dominant Mutation in Nuclear Receptor Interacting Protein 1 Causes Urinary Tract Malformations  Dysregulation of Retinoic Acid Signaling.},
	journal = {J Am Soc Nephrol},
	volume = {28},
	year = {2017},
	month = {2017 Aug},
	pages = {2364-2376},
	abstract = {<p>Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of CKD in the first three decades of life. However, for most patients with CAKUT, the causative mutation remains unknown. We identified a kindred with an autosomal dominant form of CAKUT. By whole-exome sequencing, we identified a heterozygous truncating mutation (c.279delG, p.Trp93fs*) of the nuclear receptor interacting protein 1 gene () in all seven affected members.  encodes a nuclear receptor transcriptional cofactor that directly interacts with the retinoic acid receptors (RARs) to modulate retinoic acid transcriptional activity. Unlike wild-type NRIP1, the altered NRIP1 protein did not translocate to the nucleus, did not interact with RAR, and failed to inhibit retinoic acid-dependent transcriptional activity upon expression in HEK293 cells. Notably, we also showed that treatment with retinoic acid enhanced NRIP1 binding to RAR RNA  hybridization confirmed  expression in the developing urogenital system of the mouse. In explant cultures of embryonic kidney rudiments, retinoic acid stimulated  expression, whereas a pan-RAR antagonist strongly reduced it. Furthermore, mice heterozygous for a null allele of  showed a CAKUT-spectrum phenotype. Finally, expression and knockdown experiments in  confirmed an evolutionarily conserved role for  in renal development. These data indicate that dominant  mutations can cause CAKUT by interference with retinoic acid transcriptional signaling, shedding light on the well documented association between abnormal vitamin A levels and renal malformations in humans, and suggest a possible gene-environment pathomechanism in this disease.</p>},
	keywords = {Adaptor Proteins, Signal Transducing, Animals, Mice, Mutation, Nuclear Proteins, Nuclear Receptor Interacting Protein 1, Signal Transduction, Tretinoin, Urinary Tract},
	issn = {1533-3450},
	doi = {10.1681/ASN.2016060694},
	author = {Vivante, Asaf and Mann, Nina and Yonath, Hagith and Weiss, Anna-Carina and Getwan, Maike and Kaminski, Michael M and Bohnenpoll, Tobias and Teyssier, Catherine and Chen, Jing and Shril, Shirlee and van der Ven, Amelie T and Ityel, Hadas and Schmidt, Johanna Magdalena and Widmeier, Eugen and Bauer, Stuart B and Sanna-Cherchi, Simone and Gharavi, Ali G and Lu, Weining and Magen, Daniella and Shukrun, Rachel and Lifton, Richard P and Tasic, Velibor and Stanescu, Horia C and Cavaill{\`e}s, Vincent and Kleta, Robert and Anikster, Yair and Dekel, Benjamin and Kispert, Andreas and Lienkamp, Soeren S and Hildebrandt, Friedhelm}
}
@article {138,
	title = {Mutations in TBX18 Cause Dominant Urinary Tract Malformations via Transcriptional Dysregulation of Ureter Development.},
	journal = {Am J Hum Genet},
	volume = {97},
	year = {2015},
	month = {2015 Aug 06},
	pages = {291-301},
	abstract = {<p>Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first three decades of life. Identification of single-gene mutations that cause CAKUT permits the first insights into related disease mechanisms. However, for most cases the underlying defect remains elusive. We identified a kindred with an autosomal-dominant form of CAKUT with predominant ureteropelvic junction obstruction. By whole exome sequencing, we identified a heterozygous truncating mutation (c.1010delG) of T-Box transcription factor 18 (TBX18) in seven affected members of the large kindred. A screen of additional families with CAKUT identified three families harboring two heterozygous TBX18 mutations (c.1570C>T and c.487A>G). TBX18 is essential for developmental specification of the ureteric mesenchyme and ureteric smooth muscle cells. We found that all three TBX18 altered proteins still dimerized with the wild-type protein but had prolonged protein half life and exhibited reduced transcriptional repression activity compared to wild-type TBX18. The p.Lys163Glu substitution altered an amino acid residue critical for TBX18-DNA interaction, resulting in impaired TBX18-DNA binding. These data indicate that dominant-negative TBX18 mutations cause human CAKUT by interference with TBX18 transcriptional repression, thus implicating ureter smooth muscle cell development in the pathogenesis of human CAKUT.</p>},
	keywords = {Base Sequence, Electrophoretic Mobility Shift Assay, Exome, Gene Expression Regulation, Developmental, Genes, Dominant, HEK293 Cells, Humans, Immunohistochemistry, Immunoprecipitation, Microscopy, Fluorescence, Molecular Sequence Data, Muscle, Smooth, Mutation, Pedigree, Sequence Analysis, DNA, T-Box Domain Proteins, Ureter, Urinary Tract},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2015.07.001},
	author = {Vivante, Asaf and Kleppa, Marc-Jens and Schulz, Julian and Kohl, Stefan and Sharma, Amita and Chen, Jing and Shril, Shirlee and Hwang, Daw-Yang and Weiss, Anna-Carina and Kaminski, Michael M and Shukrun, Rachel and Kemper, Markus J and Lehnhardt, Anja and Beetz, Rolf and Sanna-Cherchi, Simone and Verbitsky, Miguel and Gharavi, Ali G and Stuart, Helen M and Feather, Sally A and Goodship, Judith A and Goodship, Timothy H J and Woolf, Adrian S and Westra, Sjirk J and Doody, Daniel P and Bauer, Stuart B and Lee, Richard S and Adam, Rosalyn M and Lu, Weining and Reutter, Heiko M and Kehinde, Elijah O and Mancini, Erika J and Lifton, Richard P and Tasic, Velibor and Lienkamp, Soeren S and J{\"u}ppner, Harald and Kispert, Andreas and Hildebrandt, Friedhelm}
}
