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10.1016/j.ajhg.2017.09.026 http://scihub22266oqcxt.onion/10.1016/j.ajhg.2017.09.026 C5673669!5673669!29100091     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Am+J+Hum+Genet 2017 ; 101 (5): 803-14 Nephropedia Template TP {{tp|p=29100091|t=2017. Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice |pdf=|usr=}}{{29100091}} gab.com Text Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice JO: Am J Hum Genet http://www.kidney.de/pget.php?&tw=1&pmid=29100091 #FOAvip Congenital anomalies of the kidney and urinary tract (CAKUT) constitute a major cause of chronic kidney disease in children and 20% of prenatally detected anomalies. CAKUT encompass a spectrum of developmental kidney defects, including renal agenesis, hypoplasia, and cystic and non-cystic dysplasia. More than 50 genes have been reported as mutated in CAKUT-affected case subjects. However, the pathophysiological mechanisms leading to bilateral kidney agenesis (BKA) remain largely elusive. Whole-exome or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L (growth regulation by estrogen in breast cancer 1-like), a gene reported as a target of retinoic acid signaling. Four loss-of-function and 12 damaging missense variants, 14 being absent from GnomAD, were identified. Twelve of them were present in familial or simplex BKA-affected case subjects. Female BKA-affected fetuses also displayed uterus agenesis. We demonstrated a significant association between GREB1L variants and BKA. By in situ hybridization, we showed expression of Greb1l in the nephrogenic zone in developing mouse kidney. We generated a Greb1l knock-out mouse model by CRISPR-Cas9. Analysis at E13.5 revealed lack of kidneys and genital tract anomalies in male and female Greb1l?/? embryos and a slight decrease in ureteric bud branching in Greb1l+/? embryos. We showed that Greb1l invalidation in mIMCD3 cells affected tubulomorphogenesis in 3D-collagen culture, a phenotype rescued by expression of the wild-type human protein. This demonstrates that GREB1L plays a major role in early metanephros and genital development in mice and humans. Twit Text FOAVip Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice ????Am J Hum Genet http://www.kidney.de/pget.php?&tw=1&pmid=29100091 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29100091 #FOAvip English Wikipedia <ref>{{Cite pmid|29100091}}</ref> Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice #MMPMID29100091 De Tomasi L; David P; Humbert C; Silbermann F; Arrondel C; Tores F; Fouquet S; Desgrange A; Niel O; Bole-Feysot C; Nitschké P; Roume J; Cordier MP; Pietrement C; Isidor B; Khau Van Kien P; Gonzales M; Saint-Frison MH; Martinovic J; Novo R; Piard J; Cabrol C; Verma IC; Puri R; Journel H; Aziza J; Gavard L; Said-Menthon MH; Heidet L; Saunier S; Jeanpierre C Am J Hum Genet 2017[Nov]; 101 (5): 803-14 PMID29100091show ga Congenital anomalies of the kidney and urinary tract (CAKUT) constitute a major cause of chronic kidney disease in children and 20% of prenatally detected anomalies. CAKUT encompass a spectrum of developmental kidney defects, including renal agenesis, hypoplasia, and cystic and non-cystic dysplasia. More than 50 genes have been reported as mutated in CAKUT-affected case subjects. However, the pathophysiological mechanisms leading to bilateral kidney agenesis (BKA) remain largely elusive. Whole-exome or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L (growth regulation by estrogen in breast cancer 1-like), a gene reported as a target of retinoic acid signaling. Four loss-of-function and 12 damaging missense variants, 14 being absent from GnomAD, were identified. Twelve of them were present in familial or simplex BKA-affected case subjects. Female BKA-affected fetuses also displayed uterus agenesis. We demonstrated a significant association between GREB1L variants and BKA. By in situ hybridization, we showed expression of Greb1l in the nephrogenic zone in developing mouse kidney. We generated a Greb1l knock-out mouse model by CRISPR-Cas9. Analysis at E13.5 revealed lack of kidneys and genital tract anomalies in male and female Greb1l?/? embryos and a slight decrease in ureteric bud branching in Greb1l+/? embryos. We showed that Greb1l invalidation in mIMCD3 cells affected tubulomorphogenesis in 3D-collagen culture, a phenotype rescued by expression of the wild-type human protein. This demonstrates that GREB1L plays a major role in early metanephros and genital development in mice and humans. äMutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice(epmc).pdf DeepDyve Pubget Overpricing