{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T21:22:56Z","timestamp":1787088176457,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201013\u2010PDOC\u20100029"],"award-info":[{"award-number":["ANR\u201013\u2010PDOC\u20100029"]}],"id":[{"id":"10.13039\/501100001665","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":[[2022,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To describe clinical and molecular findings in a French multicenter cohort of fetuses with prenatal diagnosis of congenital abnormality and suspicion of a localized overgrowth disorder (LOD) suggestive of genetic variants in the PI3K\u2010AKT\u2010mTOR signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed retrospectively data obtained between 1 January 2013 and 1 May 2020 from fetuses with brain and\/or limb overgrowth referred for molecular diagnosis of PI3K\u2010AKT\u2010mTOR\u2009pathway genes by next\u2010generation sequencing (NGS) using pathological tissue obtained by fetal autopsy. We also assessed the diagnostic yield of amniotic fluid.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During the study period, 21 subjects with LOD suspected of being secondary to a genetic variant of the PI3K\u2010AKT\u2010mTOR pathway were referred for analysis. Of these, 17 fetuses had brain overgrowth, including six with isolated megalencephaly (MEG) and 11 with hemimegalencephaly (HMEG). Of the six with MEG, germline variants were identified\u2009in four cases, in either\n                      <jats:italic>PIK3R2<\/jats:italic>\n                      ,\n                      <jats:italic>AKT3<\/jats:italic>\n                      or\n                      <jats:italic>MTOR<\/jats:italic>\n                      , and a postzygotic\n                      <jats:italic>PIK3R2<\/jats:italic>\n                      variant was found in the other two cases. Of the 11 with HMEG, a postzygotic\u00a0\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      \u00a0variant was found in three fetuses with extracerebral features of\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      \u2010related overgrowth spectrum, and in seven fetuses with isolated HMEG. No pathogenic variant was identified in the 11\n                      <jats:sup>th<\/jats:sup>\n                      case with HMEG. Four fetuses with limb overgrowth also had one or more lymphatic malformations (LM) and harbored a\u2009postzygotic\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      \u00a0variant.\u00a0NGS on cultured amniocytes performed in 10\u2009cases, of which nine had been found positive on analysis of pathological fetal tissue, showed variants in four, in either\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      ,\n                      <jats:italic>PIK3R2<\/jats:italic>\n                      or\n                      <jats:italic>AKT3<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Isolated MEG or HMEG may lead to identification of genetic variants in the PI3K\u2010AKT\u2010mTOR signaling pathway. Cases of limb overgrowth and LM or isolated HMEG are likely associated with\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      variants. \u00a9 2021 International Society of Ultrasound in Obstetrics and Gynecology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/uog.23715","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T06:35:05Z","timestamp":1624602905000},"page":"532-542","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Clinical and molecular data in cases of prenatal localized overgrowth disorder: major implication of genetic variants in\n                    <scp>PI3K\u2010AKT\u2010mTOR<\/scp>\n                    signaling 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