{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:27:58Z","timestamp":1786609678185,"version":"build-2736575974"},"reference-count":5,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The diagnosis of a genetic etiology for fetal akinesia deformation sequence (FADS) in the prenatal setting is challenging. It is especially difficult in patients from isolated populations in which genetic testing has been limited and the background allelic frequencies are unknown. Lethal congenital contracture syndromes type 3 (LCCS3; OMIM 611369) is a rare autosomal recessive condition caused by biallelic pathogenic variants in the\n                    <jats:italic>PIP5K1C<\/jats:italic>\n                    gene. There are only 13 cases of LCCS3 in the medical literature. We describe three cases sharing a novel variant in\n                    <jats:italic>PIP5K1C<\/jats:italic>\n                    in an isolated Canadian population and provide the first detailed postnatal phenotyping of the condition in live born neonates. The repeatedly observed variant in the\n                    <jats:italic>PIP5K1C<\/jats:italic>\n                    gene and identification of three apparently unrelated cases suggest the possibility of a founder effect in this population. These cases add to our understanding of an ultra\u2010rare genetic condition and provide personalized management in this underserviced population.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70267","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T07:37:48Z","timestamp":1786606668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lethal Congenital Contracture Syndrome Type 3 in an Isolated Canadian Population"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3382-7480","authenticated-orcid":false,"given":"Melissa J.","family":"MacPherson","sequence":"first","affiliation":[{"name":"Department of Medical Genetics University of Alberta  Edmonton Alberta Canada"},{"name":"Maternal Fetal Medicine Clinic Royal Alexandra Hospital  Edmonton Alberta Canada"},{"name":"Women and Children's Research Institute University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary C.","family":"Nash","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Y.","family":"Niederhoffer","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Alberta  Edmonton Alberta Canada"},{"name":"Maternal Fetal Medicine Clinic Royal Alexandra Hospital  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison J.","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Alberta  Edmonton Alberta Canada"},{"name":"Maternal Fetal Medicine Clinic Royal Alexandra Hospital  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Lui","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Alberta  Edmonton Alberta Canada"},{"name":"Maternal Fetal Medicine Clinic Royal Alexandra Hospital  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Doonanco","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Alberta  Edmonton Alberta Canada"},{"name":"Maternal Fetal Medicine Clinic Royal Alexandra Hospital  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trina","family":"Stryker","sequence":"additional","affiliation":[{"name":"Maternal Fetal Medicine Clinic Royal Alexandra Hospital  Edmonton Alberta Canada"},{"name":"Department of Obstetrics and Gynecology University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3396-6456","authenticated-orcid":false,"given":"Oana","family":"Caluseriu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Alberta  Edmonton Alberta Canada"},{"name":"Maternal Fetal Medicine Clinic Royal Alexandra Hospital  Edmonton Alberta Canada"},{"name":"Women and Children's Research Institute University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"issue":"7007","key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature02896","article-title":"Impaired Ptdlns(4,5)P2 Synthesis in Nerve Terminals Produces Defects in Synaptic Vesicle Trafficking","volume":"431","author":"Di Paolo G.","year":"2004","journal-title":"Nature"},{"issue":"1","key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"112654","DOI":"10.1016\/j.yexcr.2021.112654","article-title":"Phospholipase D and Phosphatidylinositol\u20104\u2010Phosphate 5\u2010Kinase 1 Are Involved in the Regulation of Oligodendrocyte Morphological Differentiation","volume":"405","author":"Kato Y.","year":"2021","journal-title":"Experimental Cell Research"},{"issue":"3","key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1086\/520771","article-title":"Lethal Contractural Syndrome Type 3 (LCCS3) is Caused by a Mutation in PIP5K1C, Which Encodes PIPKI\u03b3 of the Phophatidylinsitol Pathway","volume":"81","author":"Narkis G.","year":"2007","journal-title":"American Journal of Human Genetics"},{"issue":"7","key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/gim.2015.148","article-title":"Clinical Application of Whole\u2010Exome Sequencing Across Clinical Indications","volume":"18","author":"Retterer K.","year":"2016","journal-title":"Genetics in Medicine"},{"issue":"1","key":"e_1_2_6_6_1","first-page":"1","article-title":"Novel PIP5K1C Variant Identified in a Chinese Pedigree With Lethal Congenital Contractural Syndrome 3","volume":"24","author":"Zhang F.","year":"2024","journal-title":"BMC Pediatrics"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70267","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70267","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T07:37:49Z","timestamp":1786606669000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":5,"alternative-id":["10.1002\/ajmg.a.70267"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70267","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]},"assertion":[{"value":"2026-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.a.70267"}}