{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:59:09Z","timestamp":1790402349994,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R01EY034398"],"award-info":[{"award-number":["NIH R01EY034398"]}],"id":[{"id":"10.13039\/100000002","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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bi\u2010allelic\n                    <jats:italic>MED16<\/jats:italic>\n                    variants underlie the recently described MEDopathy termed Guillouet\u2010Gordon syndrome (GGNS, MIM #621220), characterized by neurodevelopmental and structural anomalies. To date, 27 individuals with GGNS have been reported, collectively harboring 28 distinct compound heterozygous or homozygous\n                    <jats:italic>MED16<\/jats:italic>\n                    variants. Here we present a male infant, born to unrelated parents, presenting with multiple congenital anomalies overlapping with the established GGNS phenotypic spectrum. Specifically, the clinical presentation included structural brain defects and neurodevelopmental deficits alongside significant craniofacial (microretrognathia, cleft palate, auricular\/nasal features), cardiac (double outlet right ventricle), renal (horseshoe kidney), ocular (colobomatous microphthalmia), and hand\/foot (syndactyly, nail hypoplasia) anomalies, fetal growth restriction, neonatal respiratory distress, and premature death in the first month of life. Notably, while different outer ear anomalies have been previously described in GGNS, the severe bilateral microtia and post\u2010auricular skin tag identified in this individual extend the known clinical spectrum of the syndrome. Trio exome analysis identified a novel likely pathogenic homozygous missense variant in\n                    <jats:italic>MED16<\/jats:italic>\n                    , c.1573C&gt;T p.(Arg525Trp). The p.(Arg525Trp) variant shows a relatively high population frequency (0.00025 in gnomAD v4.1), with no homozygotes identified to date. The elevated carrier frequency of this and other\n                    <jats:italic>MED16<\/jats:italic>\n                    variants suggests a potential role in additional individuals with unexplained multiple congenital anomalies.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70315","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:02:16Z","timestamp":1790398936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Guillouet\u2010Gordon Syndrome With Severe Microtia in an Infant With a Homozygous Variant in\n                    <scp>\n                      <i>MED16<\/i>\n                    <\/scp>"],"prefix":"10.1002","author":[{"given":"Sarah E.","family":"Seese","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5098-6336","authenticated-orcid":false,"given":"Linda M.","family":"Reis","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Genchanok","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Brodner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children's Research Institute Medical College of Wisconsin and Children's Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2813-441X","authenticated-orcid":false,"given":"Jessica A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Leuthner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children's Research Institute Medical College of Wisconsin and Children's Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Muriello","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children's Research Institute Medical College of Wisconsin and Children's Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0531-3586","authenticated-orcid":false,"given":"Elena V.","family":"Semina","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Medical College of Wisconsin  Milwaukee Wisconsin USA"},{"name":"Department of Pediatrics and Children's Research Institute Medical College of Wisconsin and Children's Wisconsin  Milwaukee Wisconsin USA"},{"name":"Department of Cell Biology, Neurobiology and Anatomy Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg3074"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010015\u20101541\u2010x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2025.101402"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006045\u20100"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg0635"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7492"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2025.02.016"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1206638"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2025.04.004"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/10556656241310101"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010023\u201000630\u20109"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad989"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.115"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24088"}],"container-title":["American 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