{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:59:33Z","timestamp":1789955973905,"version":"4.0.1"},"reference-count":11,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T00:00:00Z","timestamp":1476748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["01GM1211A CRANIRARE-2"],"award-info":[{"award-number":["01GM1211A CRANIRARE-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>Heterozygous germline mutations in <jats:italic>MTOR<\/jats:italic> have been shown to underlie Smith\u2013Kingsmore syndrome, a rare autosomal dominant syndrome characterized by macrocephaly, developmental delay, and dysmorphic facial features. Recently, two unrelated families with the <jats:italic>MTOR<\/jats:italic> mutation, c.5395G&gt;A p.(Glu1799Lys), were reported. Here, we describe siblings from a non\u2010consanguineous German family in whom we identified the same heterozygous missense mutation in <jats:italic>MTOR<\/jats:italic>. Remarkably, in all reported families with Smith\u2013Kingsmore syndrome and the <jats:italic>MTOR<\/jats:italic> c.5395G&gt;A mutation, including the family described herein, healthy parents of recurrently affected children do not have detectable levels of the mutation in tested tissues, lending credence to gonadal mosaicism as the underlying mechanism. Furthermore, the glutamic acid at position 1799 was shown to present a recurrent somatic mutation site in several cancers, including colon cancer, pointing to a somatic mutational hotspot in <jats:italic>MTOR<\/jats:italic>. Importantly, we highlight the occurrence of multiple intestinal polyps in the older sibling. Further patients are required to establish definitively whether polyp formation forms part of the SKS clinical spectrum. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37999","type":"journal-article","created":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T06:10:03Z","timestamp":1476771003000},"page":"264-267","source":"Crossref","is-referenced-by-count":19,"title":["Smith\u2013Kingsmore syndrome: A third family with the <i>MTOR<\/i> mutation c.5395G&gt;A p.(Glu1799Lys) and evidence for paternal gonadal mosaicism"],"prefix":"10.1002","volume":"173","author":[{"given":"Shahida","family":"Moosa","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"B\u00f6hrer\u2010Rabel","sequence":"additional","affiliation":[{"name":"Genetikum Neu\u2010Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Altm\u00fcller","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"},{"name":"Institute of Human Genetics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Beleggia","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6khan","family":"Yigit","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Wollnik","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,10,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1089943"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37070"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.07.003"},{"key":"e_1_2_8_5_1","first-page":"1993","volume-title":"GeneReviews\u00ae [Internet]","author":"Eng C","year":"2001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1075"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1212704"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.06.061"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.0363"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-015-0240-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/302322"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.4137\/JGE.S12583"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37999","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37999","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37999","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T15:00:09Z","timestamp":1696604409000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,18]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1002\/ajmg.a.37999"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37999","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,18]]}}}