{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T22:11:11Z","timestamp":1792534271703,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2023,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary lymphedema 1 is a rare congenital condition, characterized by the development of chronic swelling in body parts. It is highly variable in expression and age of onset with different presentations: from feet edema to hydrops fetalis. This affection is genetically heterogeneous with autosomal dominant inheritance and incomplete penetrance due to a mutation in the <jats:italic>FLT4<\/jats:italic> gene in most cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Cases<\/jats:title><jats:p>In our study, we report on two fetuses harboring congenital lymphedema with <jats:italic>FLT4<\/jats:italic> variation and review the prenatal confirmed ones of the literatures. Our cases were selected within fetuses explored by exome sequencing in a diagnosis setting. Prenatal ultrasonography showed hydrops fetalis in one case and an increased nuchal translucency with hydrothorax in the other. Comparative genomic hybridization array on amniocentesis was normal in both cases. Exome sequencing identified a variation p.(Ser1275Thr) and p.(Ser1275Arg) in fetus 1 and fetus 2 in the <jats:italic>FLT4<\/jats:italic> gene, respectively. A <jats:italic>de novo<\/jats:italic> mutation at the same codon was reported in prenatal literature suggesting possible genotype phenotype correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Cystic hygroma\/hydrops fetalis are possible manifestations of several disorders. This study illustrates how the integration of exome sequencing in prenatal clinical practice can facilitate the diagnosis and genetic counseling of heterogeneous developmental affections.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2141","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T23:09:35Z","timestamp":1671577775000},"page":"563-571","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Two novel variations p.(<scp>Ser1275Thr<\/scp>) and p.(<scp>Ser1275Arg<\/scp>) in <scp><i>FLT4<\/i><\/scp> causing prenatal hereditary lymphedema type 1"],"prefix":"10.1002","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-4303","authenticated-orcid":false,"given":"Yosra","family":"Lajmi","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine of System and Organs Diseases Cochin Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Loeuillet","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Petrilli","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Egloff","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Nectoux","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of System and Organs Diseases Cochin Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Molac","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Maternity Port\u2010Royal APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Roux","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3490-2144","authenticated-orcid":false,"given":"Emmanuelle","family":"Pannier","sequence":"additional","affiliation":[{"name":"Gynecology\u2010Obstetrics Department Port\u2010Royal Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amale","family":"Achaiaa","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaina Ait","family":"Arkoub","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Chuon","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Coussement","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of System and Organs Diseases Cochin Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9680-3662","authenticated-orcid":false,"given":"Jean Michel","family":"Dupont","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of System and Organs Diseases Cochin Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3450-4958","authenticated-orcid":false,"given":"Val\u00e9rie","family":"Malan","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Spaggiari","sequence":"additional","affiliation":[{"name":"Gynecology\u2010Obstetrics Department Necker Hospital for Children Diseases, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferechte","family":"Razavi","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5973-4728","authenticated-orcid":false,"given":"Jeanne","family":"Amiel","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Bessi\u00e8res","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Grotto","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Maternity Port\u2010Royal APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1155-3626","authenticated-orcid":false,"given":"Tania","family":"Atti\u00e9\u2010Bitach","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine of Rare Disorders Necker Hospital, APHP Center, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.03.006"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.024802"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71614"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-008-0586-5"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1237"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304499200"},{"key":"e_1_2_7_8_1","first-page":"1","article-title":"Hereditary disorders of the lymphatic system and varicose veins","volume":"12","author":"Ferrell R. E.","year":"2013","journal-title":"Emery and Rimoin's Principles and Practice of Medical Genetics"},{"issue":"5","key":"e_1_2_7_9_1","first-page":"1233","article-title":"The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor","volume":"8","author":"Galland F.","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2011.01.041"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00687.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22223"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20010201)98:4<303::AID-AJMG1113>3.0.CO;2-9"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac9396"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3970"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2003.235"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.16"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.418"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2014.0044"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1549-8719.2010.00030.x"},{"key":"e_1_2_7_21_1","first-page":"505","article-title":"An undescribed variety of hereditary oedema","volume":"56","author":"Milroy W. F.","year":"1892","journal-title":"Medizinhistorisches Journal"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313250"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0260-9"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62643"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0709-8"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2023643"},{"key":"e_1_2_7_28_1","volume-title":"GeneReviews\u00ae","author":"Zanten M.","year":"1993"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0750-4"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00206"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.2141","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bdr2.2141","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.2141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T01:16:00Z","timestamp":1697073360000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.2141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,20]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,3,15]]}},"alternative-id":["10.1002\/bdr2.2141"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.2141","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"value":"2472-1727","type":"print"},{"value":"2472-1727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,20]]},"assertion":[{"value":"2022-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}