{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:19:27Z","timestamp":1790680767177,"version":"4.1.0"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS096173"],"award-info":[{"award-number":["R01NS096173"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp;amp; Gyne"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pathogenic variants of collagen type IV alpha 1 and 2 (\n                    <jats:italic>COL4A1\/COL4A2<\/jats:italic>\n                    ) genes cause various phenotypic anomalies, including intracerebral hemorrhage and a wide spectrum of developmental anomalies. Only 20% of fetuses referred for\n                    <jats:italic>COL4A1\/COL4A2<\/jats:italic>\n                    molecular screening (fetuses with a suspected intracerebral hemorrhage) carry a pathogenic variant in these genes, raising questions regarding the causative anomaly in the remaining 80% of these fetuses. We examined, following termination of pregnancy or\n                    <jats:italic>in\u2010utero<\/jats:italic>\n                    fetal death, a series of 113 unrelated fetuses referred for\n                    <jats:italic>COL4A1\/COL4A2<\/jats:italic>\n                    molecular screening, in which targeted sequencing was negative. Using exome sequencing data and a gene\u2010based collapsing test, we searched for enrichment of rare qualifying variants in our fetal cohort in comparison to the Genome Aggregation Database (gnomAD) control cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200971\u2009702). Qualifying variants in pyruvate dehydrogenase E1 subunit alpha 1 (\n                    <jats:italic>PDHA1<\/jats:italic>\n                    ) were overrepresented in our cohort, reaching genome\u2010wide significance (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20092.11\u2009\u00d7\u200910\n                    <jats:sup>\u20137<\/jats:sup>\n                    ). Heterozygous\n                    <jats:italic>PDHA1<\/jats:italic>\n                    loss\u2010of\u2010function variants were identified in three female fetuses. Among these three cases, we observed microcephaly, ventriculomegaly, germinolytic pseudocysts, agenesis\/dysgenesis of the corpus callosum and white\u2010matter anomalies that initially suggested cerebral hypoxic\u2010ischemic and hemorrhagic lesions. However, a careful\n                    <jats:italic>a\u2010posteriori<\/jats:italic>\n                    reanalysis of imaging and postmortem data showed that the observed lesions were also consistent with those observed in fetuses carrying\n                    <jats:italic>PDHA1<\/jats:italic>\n                    pathogenic variants, strongly suggesting that these two phenotypes may overlap. Exome sequencing should therefore be performed in fetuses referred for\n                    <jats:italic>COL4A1\/COL4A2<\/jats:italic>\n                    molecular screening which are screen\u2010negative, with particular attention paid to the\n                    <jats:italic>PDHA1<\/jats:italic>\n                    gene. \u00a9 2022 International Society of Ultrasound in Obstetrics and Gynecology.\n                  <\/jats:p>","DOI":"10.1002\/uog.26046","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T12:19:49Z","timestamp":1660047589000},"page":"805-811","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Rare metabolic disease mimicking\n                    <i>\n                      <scp>COL4A1<\/scp>\n                      \/\n                      <scp>COL4A2<\/scp>\n                    <\/i>\n                    fetal brain phenotype"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5610-7411","authenticated-orcid":false,"given":"T.","family":"Coste","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, NeuroDiderot  Paris France"},{"name":"Service de G\u00e9n\u00e9tique Mol\u00e9culaire Neurovasculaire AP\u2010HP, H\u00f4pital Saint\u2010Louis  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Aloui","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, NeuroDiderot  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Petit","sequence":"additional","affiliation":[{"name":"CHU Lille, Clinique de G\u00e9n\u00e9tique Guy Fontaine  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Moutton","sequence":"additional","affiliation":[{"name":"Centre Pluridisciplinaire de Diagnostic Pr\u00e9natal, MSP Bordeaux Bagatelle  Talence France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Devisme","sequence":"additional","affiliation":[{"name":"CHU Lille, Institut de Pathologie  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. F.","family":"Wells","sequence":"additional","affiliation":[{"name":"CHU Montpellier, D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale et F\u0153topathologie  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Leboucq","sequence":"additional","affiliation":[{"name":"CHU Montpellier, D\u00e9partement de Neuroradiologie Neuroradiologie Diagnostique P\u00e9diatrique  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Verpillat","sequence":"additional","affiliation":[{"name":"CHU Lille, Service de Radiologie  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Yvert","sequence":"additional","affiliation":[{"name":"Centre Pluridisciplinaire de Diagnostic Pr\u00e9natal, MSP Bordeaux Bagatelle  Talence France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Rivier","sequence":"additional","affiliation":[{"name":"CHU Montpellier, D\u00e9partement de Neurologie P\u00e9diatrique, PhyMedExp, Universit\u00e9 de Montpellier, INSERM, CNRS  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Tournier\u2010Lasserve","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, NeuroDiderot  Paris France"},{"name":"Service de G\u00e9n\u00e9tique Mol\u00e9culaire Neurovasculaire AP\u2010HP, H\u00f4pital Saint\u2010Louis  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.08.008"},{"key":"e_1_2_5_3_1","volume-title":"GeneReviews\u00ae","author":"Ganetzky R","year":"1993"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.09.001"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-0011-5"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12463"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlv022"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006567"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2020-106896"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23736"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.210"}],"container-title":["Ultrasound in Obstetrics &amp; Gynecology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/uog.26046","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/uog.26046","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/uog.26046","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T08:41:36Z","timestamp":1779093696000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/uog.26046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":10,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/uog.26046"],"URL":"https:\/\/doi.org\/10.1002\/uog.26046","archive":["Portico"],"relation":{},"ISSN":["0960-7692","1469-0705"],"issn-type":[{"value":"0960-7692","type":"print"},{"value":"1469-0705","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12]]},"assertion":[{"value":"2022-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}