{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:51:18Z","timestamp":1784206278231,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal translucency (50%), and fetal hydrops (35%). Postmortem examinations unveiled additional anomalies including facial dysmorphisms, dysplastic skeletal changes, ichthyosis, multiple pterygia, and myopathy, allowing preliminary diagnosis of particular Mendelian disorders in multiple patients. Evaluation of the parents revealed maternal grip myotonia in one family. By exome sequencing and targeted testing, we identified causative variants in\n                    <jats:italic>ACTC1, CHST14, COG6, DMPK, DOK7, HSPG2, KLHL7, KLHL40, KIAA1109, NEB, PSAT1, RAPSN, USP14<\/jats:italic>\n                    , and\n                    <jats:italic>WASHC5<\/jats:italic>\n                    in 15 families, and one patient with a plausible diagnosis associated with biallelic\n                    <jats:italic>NEB<\/jats:italic>\n                    variants\n                    <jats:italic>.<\/jats:italic>\n                    Three patients received a dual diagnosis\n                    <jats:italic>.<\/jats:italic>\n                    Pathogenic alterations in newly discovered genes or in previously known genes recently linked to new MCC phenotypes were observed in 44% of the cohort. Our results provide new insights into the clinical and molecular landscape of lethal MCC phenotypes.\n                  <\/jats:p>","DOI":"10.1111\/cge.14490","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T21:43:40Z","timestamp":1706305420000},"page":"596-610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical and molecular characteristics of 26 fetuses with lethal multiple congenital contractures"],"prefix":"10.1111","volume":"105","author":[{"given":"Gozde Tutku","family":"Turgut","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umut","family":"Altunoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"},{"name":"Department of Medical Genetics Ko\u00e7 University School of Medicine (KUSoM)  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cagri","family":"Gulec","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tugba","family":"Sarac Sivrikoz","sequence":"additional","affiliation":[{"name":"Division of Perinatology, Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-5916","authenticated-orcid":false,"given":"Tu\u011fba","family":"Kalayc\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guven","family":"Toksoy","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eahin","family":"Avc\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"},{"name":"Department of Medical Genetics Ko\u00e7 University School of Medicine (KUSoM)  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behiye Tu\u011f\u00e7e","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6zde Ye\u015fil","family":"Say\u0131n","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim Halil","family":"Kalelioglu","sequence":"additional","affiliation":[{"name":"Division of Perinatology, Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birsen","family":"Karaman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"},{"name":"Department of Pediatric Basic Sciences, Institute of Child Health Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Recep","family":"Has","sequence":"additional","affiliation":[{"name":"Division of Perinatology, Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seher","family":"Ba\u015faran","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atil","family":"Yuksel","sequence":"additional","affiliation":[{"name":"Division of Perinatology, Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0376-499X","authenticated-orcid":false,"given":"H\u00fclya","family":"Kayserili","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"},{"name":"Department of Medical Genetics Ko\u00e7 University School of Medicine (KUSoM)  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2035-4338","authenticated-orcid":false,"given":"Zehra Oya","family":"Uyguner","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31721"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.03.008"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31723"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84457"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2021.03.019"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102020\u2010107595"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.05.015"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010019\u20100680\u20101"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102020\u2010106901"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5809"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010015\u20100364\u20100"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14117"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21408"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2023.100213"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.12.002"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.10.016"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22693"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.01.013"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102013\u2010101715"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201086309\u20109"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.11.004"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010009\u20105405\u2010y"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181dd43bf"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.08.003"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20100004.2007.00824.x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.6.e81"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.065425"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61473"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.11.010"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.05.026"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.004"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13745"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm239"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5616"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2009.08.012"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104624"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1449"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010019\u20100477\u20102"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0960\u20107692.2001.00512.x"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.151.2.6709916"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.13308"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14490","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T21:36:47Z","timestamp":1714599407000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14490"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,26]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1111\/cge.14490"],"URL":"https:\/\/doi.org\/10.1111\/cge.14490","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14490\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14490\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14490\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14490\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14490\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,26]]},"assertion":[{"value":"2023-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}