Abstract
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 genera...Continue Reading
Citations
Nov 6, 2018·Human Molecular Genetics·Madeline Louise ReillyAlexandre Benmerah
Aug 26, 2018·Journal of the American Society of Nephrology : JASN·Amelie T van der VenFriedhelm Hildebrandt
Feb 1, 2020·Prenatal Diagnosis·Angie C JelinEric B Jelin
May 8, 2020·Clinical Genetics·Adeline JacquinetVincent Bours
Aug 10, 2018·Nature Reviews. Nephrology·Zachary WareJoncasStephen C Ekker
Aug 20, 2019·Human Reproduction·Morten K HerlinInge S Pedersen
Aug 19, 2020·Nature Reviews. Nephrology·Emily E GroopmanAli G Gharavi
Jun 27, 2020·Genes·Isabelle SchrauwenSuzanne M Leal
Aug 21, 2020·Orphanet Journal of Rare Diseases·Morten Krogh HerlinMats Brännström
Jun 30, 2018·Human Genetics·Isabelle SchrauwenRick A Friedman
May 16, 2019·Journal of the American Society of Nephrology : JASN·Sophia Cameron-ChristieAli G Gharavi
Feb 15, 2020·Indian Journal of Pediatrics·Veronica AroraIshwar Chander Verma
Aug 2, 2020·European Journal of Human Genetics : EJHG·Helge MartensRuthild G Weber
Jul 1, 2020·Genetic Testing and Molecular Biomarkers·Ancong WangXiangyu Zhao
Oct 30, 2020·PloS One·Kris A ChristensenBen F Koop
Jan 19, 2021·Acta histochemica·Valentina LasićKatarina Vukojević
Feb 7, 2021·European Journal of Medical Genetics·Isaac Kyei Barffour, Roselind Kyei Baah Kwarkoh
Dec 10, 2020·Evolutionary Applications·Stuart C WillisShawn R Narum
Jan 15, 2021·Differentiation; Research in Biological Diversity·Rex A HessBarry T Hinton
Feb 6, 2021·Diagnostics·Daniele GuadagnoloEnrica Marchionni
Mar 26, 2021·Frontiers in Cell and Developmental Biology·Laura Santana GonzalezAhmed A Ahmed
Jun 24, 2018·The American Journal of Pathology·Osamu IchiiYasuhiro Kon
Apr 7, 2021·BMJ Case Reports·Mireia TuguesRaquel Corripio
Jun 3, 2021·Biology·Paola PontecorviCinzia Marchese
Jun 24, 2021·Disease Models & Mechanisms·Laura Santana GonzálezAhmed Ashour Ahmed
Jun 26, 2021·Scientific Reports·Yilin YuJiancheng Li
May 30, 2021·Journal of the American Society of Nephrology : JASN·Lei DaiWeishe Zhang
Jan 11, 2022·Human Mutation·Penelope JordanLaurence Heidet