{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:53:06Z","timestamp":1778683986384,"version":"3.51.4"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T00:00:00Z","timestamp":1619308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G035620N"],"award-info":[{"award-number":["G035620N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007229","name":"Bijzonder Onderzoeksfonds UGent","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007229","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We report three babies from two families with a severe lethal form of congenital cutis laxa. All three had redundant and doughy\u2010textured skin and two siblings from one family had facial dysmorphism. Echocardiograms showed thickened and poorly contractile hearts, arterial dilatation and tortuosity. Post\u2010mortem examination in two of the babies further revealed widespread ectasia and tortuosity of medium and large sized arteries, myocardial hypertrophy, rib and skull fractures. The presence of fractures initially suggested a diagnosis of osteogenesis imperfecta. Under light microscopy bony matrices were abnormal and arterial wall architecture was grossly abnormal showing fragmented elastic fibres. Molecular analysis of known cutis laxa genes did not yield any pathogenic defects. Whole exome sequencing of DNA following informed consent identified two separate homozygous variants in the\n                    <jats:italic>LOX<\/jats:italic>\n                    (Lysyl Oxidase) gene.\n                    <jats:italic>LOX<\/jats:italic>\n                    belongs to the 5\u2010lysyl oxidase gene family involved in initiation of cross\u2010linking of elastin and collagen. A mouse model of a different variant in this gene recapitulates the phenotype seen in the three babies. Our findings suggest that the\n                    <jats:italic>LOX<\/jats:italic>\n                    gene is a novel cause of severe congenital cutis laxa with arterial tortuosity, bone fragility and respiratory failure.\n                  <\/jats:p>","DOI":"10.1111\/cge.13969","type":"journal-article","created":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T03:38:38Z","timestamp":1618717118000},"page":"168-175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Severe congenital cutis laxa: Identification of novel homozygous\n                    <scp>\n                      <i>LOX<\/i>\n                    <\/scp>\n                    gene variants in two families"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4853-5269","authenticated-orcid":false,"given":"Fiona","family":"McKenzie","sequence":"first","affiliation":[{"name":"Genetic Services of Western Australia King Edward Memorial Hospital  Perth Western Australia Australia"},{"name":"School of Paediatrics and Child Health University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kym","family":"Mina","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics PathWest  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bert","family":"Callewaert","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent University Hospital  Ghent Belgium"},{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aude","family":"Beyens","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent University Hospital  Ghent Belgium"},{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"},{"name":"Department of Dermatology Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan E.","family":"Dickinson","sequence":"additional","affiliation":[{"name":"Maternal Fetal Medicine Service King Edward Memorial Hospital  Perth Western Australia Australia"},{"name":"Division of Obstetrics and Gynaecology The University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth","family":"Jevon","sequence":"additional","affiliation":[{"name":"Department of Paediatric Pathology, PathWest Perth Children's Hospital  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Papadimitriou","sequence":"additional","affiliation":[{"name":"Centre for Orthopaedic Translational Research Medical School, University of Western Australia  Nedlands Western Australia Australia"},{"name":"Pathwest Laboratories  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitte Rode","family":"Diness","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Rigshospitalet, Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Department of Clinical Medicine Copenhagen University  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesper Norman","family":"Steensberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Rigshospitalet, Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Ek","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Rigshospitalet, Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth","family":"Baynam","sequence":"additional","affiliation":[{"name":"Genetic Services of Western Australia King Edward Memorial Hospital  Perth Western Australia Australia"},{"name":"The Western Australia Register of Developmental Anomalies, Department of Health Government of Western Australia  Perth Western Australia Australia"},{"name":"School of Medicine, Division of Paediatrics and Telethon Kids Institute University of Western Australia  Perth Western Australia 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