{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:48:10Z","timestamp":1768819690323,"version":"3.49.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Oligohydramnios is not a rare prenatal finding. However, recurrent oligohydramnios is uncommon, and genetic etiology should be taken into consideration. We present two families with recurrent fetal oligohydramnios that did not respond to amnioinfusion. Rapid trio-whole-exome sequencing (WES) revealed mutations in the <jats:italic>AGT<\/jats:italic> gene in both families within 1 week. The first family had a compound heterozygous mutation with c.856 + 1G &amp;gt; T and c.857-619_1269 + 243delinsTTGCCTTGC changes. The second family had homozygous c.857-619_1269 + 243delinsTTGCCTTGC mutations. <jats:italic>AGT<\/jats:italic> gene mutation may lead to autosomal recessive renal tubular dysgenesis, a rare and lethal disorder that can result in early neonatal death. Both the alleles identified are known alleles associated with pathogenicity. Our findings suggest that trio-WES analysis may help rapidly identify causative etiologies that can inform prompt counseling and decision-making prenatally.<\/jats:p>","DOI":"10.3389\/fgene.2021.606970","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T08:15:41Z","timestamp":1624263341000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Rapid Trio Exome Sequencing for Autosomal Recessive Renal Tubular Dysgenesis in Recurrent Oligohydramnios"],"prefix":"10.3389","volume":"12","author":[{"given":"Shin-Yu","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwo-Tsann","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Hui","family":"Hung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Chou","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung-Ming","family":"Jeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting-An","family":"Yen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karine","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin-Hsiu","family":"Chien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuh-Liang","family":"Hwu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Nan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I-Jung","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ni-Chung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1097\/00006250-197907000-00005","article-title":"Fetal swallowing and voiding in relation to hydramnios.","volume":"54","author":"Abramovich","year":"1979","journal-title":"Obstet. Gynecl."},{"key":"B2","doi-asserted-by":"crossref","first-page":"5679","DOI":"10.1038\/s41598-017-06033-1","article-title":"Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families.","volume":"7","author":"Al-Mubarak","year":"2017","journal-title":"Sci. Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/pd.5102","article-title":"Promises, pitfalls and practicalities of prenatal whole exome sequencing.","volume":"38","author":"Best","year":"2018","journal-title":"Prenat. Diagn."},{"key":"B4","doi-asserted-by":"publisher","first-page":"699","DOI":"10.21037\/atm.2019.10.64","article-title":"The pathogenic AGT c.856+1G>T mutation of a patient with multiple renal cysts and hypertension.","volume":"7","author":"Chen","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1111\/cge.12301","article-title":"Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype.","volume":"86","author":"Filges","year":"2014","journal-title":"Clin. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1002\/uog.18915","article-title":"Whole exome sequencing as a diagnostic adjunct to clinical testing in fetuses with structural abnormalities.","volume":"51","author":"Fu","year":"2018","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation.","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1038\/ng1623","article-title":"Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis.","volume":"37","author":"Gribouval","year":"2005","journal-title":"Nat. Genet."},{"key":"B9","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/humu.21661","article-title":"Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis.","volume":"33","author":"Gribouval","year":"2012","journal-title":"Hum. Mutat."},{"key":"B10","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s00467-013-2480-1","article-title":"Renal tubular dysgenesis.","volume":"29","author":"Gubler","year":"2014","journal-title":"Pediatr. Nephrol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"798","DOI":"10.5858\/arpa.2016-0622-ra","article-title":"Development and validation of clinical whole-exome and whole-genome sequencing for detection of germline variants in inherited disease.","volume":"141","author":"Hegde","year":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1515\/jpm-2017-0281","article-title":"Outcomes in oligohydramnios: the role of etiology in predicting pulmonary morbidity\/mortality.","volume":"46","author":"Hesson","year":"2018","journal-title":"J. Perinat. Med."},{"key":"B13","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans.","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3390\/diagnostics9040185","article-title":"Prenatal diagnosis of autosomal recessive renal tubular dysgenesis with anhydramnios caused by a mutation in the AGT gene.","volume":"9","author":"Ma","year":"2019","journal-title":"Diagnostics (Basel)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/0002-9378(80)90457-3","article-title":"Antepartum fetal evaluation: development of a fetal biophysical profile.","volume":"136","author":"Manning","year":"1980","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B16","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.jmoldx.2020.06.008","article-title":"Improved diagnosis of rare disease patients through systematic detection of runs of homozygosity.","volume":"22","author":"Matalonga","year":"2020","journal-title":"J. Mol. Diagn."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The genome analysis toolkit: a mapreduce framework for analyzing next-generation DNA sequencing data.","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"B18","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.ajhg.2008.08.007","article-title":"Runs of homozygosity in European populations.","volume":"83","author":"McQuillan","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1016\/j.ekir.2020.08.011","article-title":"Autosomal recessive renal tubular dysgenesis caused by a founder mutation of AGT (Angiotensinogen).","volume":"5","author":"Min-Hua","year":"2020","journal-title":"Kidney Int. Rep."},{"key":"B20","first-page":"6","article-title":"Renal tubular dysgenesis in Israel: pathologist\u2019s experience and literature review.","volume":"11","author":"Moldavsky","year":"2009","journal-title":"ISR Med. Assoc. J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1097\/aog.0000000000002637","article-title":"Anhydramnios in the setting of renal malformations: the national institutes of health workshop summary.","volume":"131","author":"Moxey-Mims","year":"2018","journal-title":"Obstet. Gynecol."},{"key":"B22","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/s41467-020-20584-4","article-title":"AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data.","volume":"12","author":"Quinodoz","year":"2021","journal-title":"Nat. Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1002\/uog.15929","article-title":"Oligohydramnios in complicated and uncomplicated pregnancy: a systematic review and meta-analysis.","volume":"49","author":"Rabie","year":"2017","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1046\/j.1469-0705.1996.07020108.x","article-title":"Outcome of singleton pregnancies with severe oligohydramnios in the second and third trimesters.","volume":"7","author":"Shipp","year":"1996","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1111\/j.1471-0528.1977.tb12556.x","article-title":"Relationship between fetal urine production and amniotic fluid volume in normal pregnancy and pregnancy complicated by diabetes.","volume":"84","author":"van Otterlo","year":"1977","journal-title":"Br. J. Obstet. Gynaecol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data.","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"183","DOI":"10.7156\/v4i4p183","article-title":"Molecular and pathophysiological features of angiotensinogen: a mini review.","volume":"4","author":"Wu","year":"2011","journal-title":"N. Am. J. Med. Sci. (Boston)"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1097\/pcc.0000000000002068","article-title":"Critical trio exome benefits in-time decision-making for pediatric patients with severe illnesses.","volume":"20","author":"Wu","year":"2019","journal-title":"Pediatr. Crit. Care Med."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.606970\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T08:15:47Z","timestamp":1624263347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.606970\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,21]]},"references-count":29,"alternative-id":["10.3389\/fgene.2021.606970"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.606970","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,21]]},"article-number":"606970"}}