{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:58:47Z","timestamp":1792083527449,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T00:00:00Z","timestamp":1505174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify the underlying genetic cause for recurrent intrauterine fetal death (IUFD) of males.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole genome sequencing was performed on DNA from five healthy obligatory carrier females and an unaffected male offspring of a multigenerational pedigree with recurrent second\u2010trimester IUFD of males (<jats:italic>n<\/jats:italic>\u00a0=\u00a019). When documented, all deaths occurred at \u226420\u00a0weeks of gestation. Hydrops fetalis was diagnosed at death in the most recent case.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following variant filtering based on a recessive X\u2010linked inheritance pattern, a rare FOXP3 frameshift mutation (p.D303fs*87) that results in a premature truncation of the protein was discovered. Sanger sequencing confirmed the mutation in the affected fetus. The <jats:italic>FOXP3<\/jats:italic> gene encodes for a transcriptional regulator critical to the function of regulatory T cells. FOXP3 mutations are associated with immune dysregulation, polyendocrinopathy, enteropathy, and X\u2010linked (IPEX) syndrome which exclusively affects males and may present with a potentially life\u2010threatening complex autoimmune disorder in early childhood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Here, we demonstrate the utility of whole genome sequencing\u2010based pedigree analysis to identify the genetic cause for recurrent IUFD when chromosome studies, including microarray analysis, are normal. Further studies are needed to determine the prevalence of FOXP3\u2010mediated IUFD in males. \u00a9 2017 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.5142","type":"journal-article","created":{"date-parts":[[2017,8,18]],"date-time":"2017-08-18T10:44:09Z","timestamp":1503053049000},"page":"1040-1045","source":"Crossref","is-referenced-by-count":22,"title":["Whole genome sequencing identifies etiology of recurrent male intrauterine fetal death"],"prefix":"10.1002","volume":"37","author":[{"given":"Omar","family":"Shehab","sequence":"first","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Department of Molecular Pharmacology &amp; Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Tester","sequence":"additional","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Department of Molecular Pharmacology &amp; Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory Mayo Clinic  Rochester MN USA"},{"name":"Department of Cardiovascular Diseases\/Division of Heart Rhythm Services Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Ackerman","sequence":"additional","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Department of Molecular Pharmacology &amp; Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Susan","family":"Cowchock","sequence":"additional","affiliation":[{"name":"Center for Spirituality and Health Duke University School of Medicine  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8011-3333","authenticated-orcid":false,"given":"Michael J.","family":"Ackerman","sequence":"additional","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Department of Molecular Pharmacology &amp; Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory Mayo Clinic  Rochester MN USA"},{"name":"Department of Cardiovascular Diseases\/Division of Heart Rhythm Services Mayo Clinic  Rochester MN USA"},{"name":"Department of Pediatrics\/Division of Pediatric Cardiology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,12]]},"reference":[{"issue":"8","key":"e_1_2_7_2_1","first-page":"1","article-title":"Fetal and perinatal mortality: United States, 2013","volume":"64","author":"Macdorman MF","year":"2015","journal-title":"Natl Vital Stat Rep"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/GRF.0b013e3181ee2793"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1823"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1974"},{"key":"e_1_2_7_8_1","unstructured":"Exome Variant Server.NHLBI GO Exome Sequencing Project (ESP) Seattle WA (URL:http:\/\/evs.gs.washington.edu\/EVS\/) [accessed on 28 March 2017]."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atg.2015.08.002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.575787"},{"issue":"211","key":"e_1_2_7_12_1","first-page":"1","article-title":"Immune dysregulation, polyendocrinopathy, enteropathy, X\u2010linked syndrome: a paradigm of immunodeficiency with autoimmunity","volume":"3","author":"Barzaghi F","year":"2012","journal-title":"Front Immunol"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2014.12.007"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-1188"},{"key":"e_1_2_7_16_1","first-page":"1","article-title":"From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation","author":"Bacchetta R","year":"2016","journal-title":"Ann N Y Acad Sci"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.13076"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05479"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1437"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2006.04.007"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2009.11.020"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gah044"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2007.03.037"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-100759"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.09.006"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37401"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60773-5"}],"container-title":["Prenatal Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpd.5142","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.5142","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T15:51:36Z","timestamp":1696002696000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.5142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,12]]},"references-count":26,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1002\/pd.5142"],"URL":"https:\/\/doi.org\/10.1002\/pd.5142","archive":["Portico"],"relation":{},"ISSN":["0197-3851","1097-0223"],"issn-type":[{"value":"0197-3851","type":"print"},{"value":"1097-0223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,12]]}}}