{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:50:57Z","timestamp":1783731057194,"version":"3.55.0"},"reference-count":13,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,3,3]],"date-time":"2018-03-03T00:00:00Z","timestamp":1520035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Bambino Ges\u00f9 Onlus","award":["Vite Coraggiose research project"],"award-info":[{"award-number":["Vite Coraggiose research project"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly\u2013hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45 cases from 27 families have been reported, and the pathogenic bi\u2010allelic mutations in <jats:italic><jats:styled-content style=\"fixed-case\">FLVCR<\/jats:styled-content>2<\/jats:italic> gene described in 15 families. The pathogenesis of this condition has not been fully elucidated so far.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report on an additional family with two affected fetuses carrying a novel homozygous mutation in <jats:italic><jats:styled-content style=\"fixed-case\">FLVCR<\/jats:styled-content>2<\/jats:italic> gene, and describe the impact of known mutants on the protein structural and functional impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The present report confirms the genetic homogeneity of Fowler syndrome and describes a new <jats:italic><jats:styled-content style=\"fixed-case\">FLVCR<\/jats:styled-content>2<\/jats:italic> mutation affecting the protein function. The structural analysis of the present and previously published <jats:italic><jats:styled-content style=\"fixed-case\">FLVCR<\/jats:styled-content>2<\/jats:italic> mutations supports the hypothesis of a reduced heme import as the underlying disease's mechanism due to the stabilization of the occluded conformation or a protein misfolding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest the hypothesis of heme deficiency as the major pathogenic mechanism of Fowler syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.376","type":"journal-article","created":{"date-parts":[[2018,3,3]],"date-time":"2018-03-03T05:06:37Z","timestamp":1520053597000},"page":"446-451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Proliferative vasculopathy and hydranencephaly\u2013hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1993-8018","authenticated-orcid":false,"given":"Francesca Clementina","family":"Radio","sequence":"first","affiliation":[{"name":"Genetics and Rare Diseases Research Area Bambino Ges\u00f9 Children's Hospital IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavinia","family":"Di Meglio","sequence":"additional","affiliation":[{"name":"Federico II University Naples Italy"},{"name":"Ultrasound and Prenal Diagnosis \u201cAniello Di Meglio\u201d Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6543-6225","authenticated-orcid":false,"given":"Emanuele","family":"Agolini","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Bambino Ges\u00f9 Children's Hospital IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Bellacchio","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Area Bambino Ges\u00f9 Children's Hospital IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Rinelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Bambino Ges\u00f9 Children's Hospital IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Toscano","sequence":"additional","affiliation":[{"name":"Federico II University Naples Italy"},{"name":"Ultrasound and Prenal Diagnosis \u201cAniello Di Meglio\u201d Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Boldrini","sequence":"additional","affiliation":[{"name":"Pathology Unit Bambino Ges\u00f9 Children's Hospital IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Bambino Ges\u00f9 Children's Hospital IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniello","family":"Di Meglio","sequence":"additional","affiliation":[{"name":"Federico II University Naples Italy"},{"name":"Ultrasound and Prenal Diagnosis \u201cAniello Di Meglio\u201d Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Dallapiccola","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Area Bambino Ges\u00f9 Children's Hospital IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108362200"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2003.10.002"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389901401214"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00690-10"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1972.tb02575.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087619"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.085"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12565"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21293"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.02.004"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21329"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv485"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33094"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.376","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.376","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T15:29:42Z","timestamp":1695396582000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,3]]},"references-count":13,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1002\/mgg3.376"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.376","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,3]]},"assertion":[{"value":"2017-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}