{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:08:12Z","timestamp":1773295692207,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T00:00:00Z","timestamp":1551744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN\u2010154279"],"award-info":[{"award-number":["FDN\u2010154279"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010787","name":"Genome Alberta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000233","name":"Genome British Columbia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000233","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000092","name":"Ontario Genomics Institute","doi-asserted-by":"publisher","award":["OGI\u2010147"],"award-info":[{"award-number":["OGI\u2010147"]}],"id":[{"id":"10.13039\/501100000092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:p>Neu\u2013Laxova syndrome (NLS) is a lethal autosomal recessive microcephaly syndrome associated with intrauterine growth restriction (IUGR) and multiple congenital anomalies. Clinical features include central nervous system malformations, joint contractures, ichthyosis, edema, and dysmorphic facial features. Biallelic pathogenic variants in either the <jats:italic>PHGDH<\/jats:italic> or <jats:italic>PSAT1<\/jats:italic> genes have been shown to cause NLS. Using exome sequencing, we aimed to identify the underlying genetic diagnosis in three fetuses (from one family) with prenatal skin edema, severe IUGR, micrognathia, renal anomalies, and arthrogryposis and identified a homozygous c.1A&gt;C (p.Met1?, NM_006623.3) variant in the <jats:italic>PHGDH<\/jats:italic> gene. Loss of the translation start codon is a novel genetic mechanism for the development of NLS. Prenatal diagnosis of NLS is challenging and few reports describe the fetal pathology. Fetal neuropathologic examination revealed: delayed brain development, congenital agenesis of the corticospinal tracts, and hypoplasia of the hippocampus, cerebellum and brainstem. Each pregnancy also showed increased nuchal translucency (NT) or cystic hygroma. While NLS is rare, it may be a cause of recurrent increased NT\/cystic hygroma. This finding provides further support that cystic hygroma has many different genetic causes and that exome sequencing may shed light on the underlying genetic diagnoses in this group of prenatal patients.<\/jats:p>","DOI":"10.1002\/ajmg.a.61076","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T07:56:03Z","timestamp":1551858963000},"page":"813-816","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Neu\u2013Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2244-6201","authenticated-orcid":false,"given":"Danielle K.","family":"Bourque","sequence":"first","affiliation":[{"name":"Regional Genetics Program, CHEO University of Ottawa  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireille","family":"Cloutier","sequence":"additional","affiliation":[{"name":"Regional Genetics Program, CHEO University of Ottawa  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin D.","family":"Kernohan","sequence":"additional","affiliation":[{"name":"CHEO Research Institute University of Ottawa  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Bareke","sequence":"additional","affiliation":[{"name":"Department of Human Genetics McGill University  Montreal Qu\u00e9bec Canada"},{"name":"McGill University and Genome Quebec Innovation Centre  Montreal Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Grynspan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine CHEO, University of Ottawa  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Michaud","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine CHEO, University of Ottawa  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Care4Rare Canada Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-8052","authenticated-orcid":false,"given":"Kym M.","family":"Boycott","sequence":"additional","affiliation":[{"name":"Regional Genetics Program, CHEO University of Ottawa  Ottawa Ontario Canada"},{"name":"CHEO Research Institute University of Ottawa  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.07.012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/15513811003620914"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.228"},{"issue":"2","key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1365-2788.1972.tb01585.x","article-title":"A further example of a lethal autosomal recessive condition in sibs","volume":"16","author":"Laxova R.","year":"1972","journal-title":"Journal of Intellectual Disability Research"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33737"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36930"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"issue":"3","key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1542\/peds.47.3.610","article-title":"A lethal syndrome of microcephaly with multiple congenital anomalies in three siblings","volume":"47","author":"Neu R. 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