{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:00:35Z","timestamp":1790618435934,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021201","name":"European Academy of Dermatology and Venereology","doi-asserted-by":"publisher","award":["EADV PPRC\u20102024\u20100022"],"award-info":[{"award-number":["EADV PPRC\u20102024\u20100022"]}],"id":[{"id":"10.13039\/501100021201","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Myhre syndrome is a rare disorder that typically results from a\n                    <jats:italic>de novo SMAD4<\/jats:italic>\n                    variant.\n                    <jats:italic>De novo SMAD4<\/jats:italic>\n                    variants have recently been shown to be associated with \u2018selfish selection\u2019 in the male germline, explaining their exclusive paternal origin and the paternal age effect reported for Myhre syndrome. Over recent years, there has been a steady increase in the number of families reported with an affected parent and child. We expand the literature of families with Myhre syndrome reporting a mildly affected 38\u2010year\u2010old mother and her 4\u2010year\u2010old son who carry the\n                    <jats:italic>SMAD4<\/jats:italic>\n                    p.Arg496Cys variant, consistent with all other reports of inherited Myhre syndrome. To better delineate the phenotypic spectrum, we developed a clinical severity score and compared familial cases to sporadic cases, revealing a milder phenotype in familial cases. Affected mothers with Myhre syndrome may be at increased risk of infertility and pregnancy loss. Since identification of the mode of transmission is essential for accurate reproductive counseling and appropriate clinical surveillance, we propose a nuanced reproductive and genetic counseling strategy that emphasizes awareness of potential autosomal dominant transmission, paternal age\u2010related risk, and obstetric complications.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.c.32161","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T07:04:56Z","timestamp":1765177496000},"page":"330-343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Autosomal Dominant Transmission Reframes Reproductive Counseling in Myhre Syndrome: A Novel Family and Literature Review"],"prefix":"10.1002","volume":"199","author":[{"given":"Maggie R.","family":"Brand","sequence":"first","affiliation":[{"name":"Medical Genetics, Department of Pediatrics Mass General for Children  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6380-2471","authenticated-orcid":false,"given":"Eva","family":"Vanbelleghem","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent University Hospital  Ghent Belgium"},{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1432-2516","authenticated-orcid":false,"given":"Alison C.","family":"Kay","sequence":"additional","affiliation":[{"name":"MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine University of Oxford  Oxford UK"},{"name":"NIHR Biomedical Research Centre  Oxford UK"},{"name":"The Center for Personalised Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9229-7216","authenticated-orcid":false,"given":"Anne","family":"Goriely","sequence":"additional","affiliation":[{"name":"MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine University of Oxford  Oxford UK"},{"name":"NIHR Biomedical Research Centre  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8374-0359","authenticated-orcid":false,"given":"Senol","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Medicine Marmara University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8397-4078","authenticated-orcid":false,"given":"Peter J.","family":"Hulick","sequence":"additional","affiliation":[{"name":"Mark R. Neaman Center for Personalized Medicine Endeavor Health  Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breanne","family":"Prindeville","sequence":"additional","affiliation":[{"name":"Mark R. Neaman Center for Personalized Medicine Endeavor Health  Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley W.","family":"Wong","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Pediatrics Mass General for Children  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9743-4205","authenticated-orcid":false,"given":"Bert","family":"Callewaert","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent University Hospital  Ghent Belgium"},{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1145-4572","authenticated-orcid":false,"given":"Angela E.","family":"Lin","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Pediatrics Mass General for Children  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201036606\u2010w"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000527149"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.12.017"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgc4.1910"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63497"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61430"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63638"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61377"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20100004.1981.tb01798.x"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63984"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010024\u201001664\u2010"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5108"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2022.10.017"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2024.07.006"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010022\u201002447\u2010x"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010018\u20100334\u2010x"}],"container-title":["American Journal of Medical Genetics Part C: Seminars in Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.32161","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.c.32161","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.32161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:48:09Z","timestamp":1790617689000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.c.32161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":16,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/ajmg.c.32161"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.c.32161","archive":["Portico"],"relation":{},"ISSN":["1552-4868","1552-4876"],"issn-type":[{"value":"1552-4868","type":"print"},{"value":"1552-4876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}