{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:36:24Z","timestamp":1791999384414,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,9,23]],"date-time":"2018-09-23T00:00:00Z","timestamp":1537660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>Nonimmune hydrops fetalis (NIHF) is a rare disorder with a high perinatal mortality of at least 50%. One cause of NIHF is generalized lymphatic dysplasia (GLD), a rare form of primary lymphedema of the extremities and systemic involvement including chylothoraces and pericardial effusions. An autosomal recessive form of GLD has been described, caused by variants in the <jats:italic>PIEZO1<\/jats:italic> gene. It has been reported clinically to cause NIHF and childhood onset of facial and limb lymphedema, most of which were diagnosed postnatally. We present a case of a woman with recurrent pregnancies affected by NIHF because of novel compound heterozygous variants in the <jats:italic>PIEZO1<\/jats:italic> gene diagnosed prenatally using exome sequencing (ES). Two variants in <jats:italic>PIEZO1<\/jats:italic> (c.3206G&gt;A and c.6208A&gt;C) were identified that were inherited from the father and mother, and are predicted to cause a nonsense and missense change, respectively, in the <jats:italic>PIEZO1<\/jats:italic> subunits. Ultrasound demonstrated severe bilateral pleural effusions, whole body edema and polyhydramnios. Histopathology revealed an increased number of lymphatic channels, many of which showed failure of luminal canalization. Sanger sequencing confirmed the same variants in a prior fetal demise. We provide phenotypic correlation with ultrasound and autopsy finding, review <jats:italic>PIEZO1<\/jats:italic> variants as a cause of GLD and discuss the uses of prenatal ES to date.<\/jats:p>","DOI":"10.1002\/ajmg.a.40533","type":"journal-article","created":{"date-parts":[[2018,9,23]],"date-time":"2018-09-23T14:35:52Z","timestamp":1537713352000},"page":"2829-2834","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Identification of novel <i>PIEZO1<\/i> variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis"],"prefix":"10.1002","volume":"176","author":[{"given":"Ilina","family":"Datkhaeva","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie A.","family":"Arboleda","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Niroshi","family":"Senaratne","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gelareh","family":"Nikpour","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherise","family":"Meyerson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yipeng","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalda","family":"Afshar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Scibetta","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Quintero\u2010Rivera","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara F.","family":"Crandall","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Prenatal Diagnosis Center David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne W.","family":"Grody","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"},{"name":"Department of Pediatrics David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"},{"name":"Department of Human Genetics David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Deignan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Janzen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology David Geffen School of Medicine, University of California Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2899"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-014-1456-y"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.484"},{"key":"e_1_2_7_5_1","first-page":"97","volume-title":"Current topics in membranes","author":"Alper S. 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