{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T12:38:01Z","timestamp":1740141481442,"version":"3.37.3"},"reference-count":17,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,4,28]],"date-time":"2018-04-28T00:00:00Z","timestamp":1524873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>Cardiofaciocutaneous (CFC) syndrome is a RASopathy characterized by intellectual disability, congenital heart defects, a characteristic facial appearance, gastro\u2010intestinal complications, ectodermal abnormalities and growth failure. The RASopathies result from germline mutations in the Ras\/Mitogen\u2010activated\u2010protein\u2010kinase (MAPK) pathway. CFC is associated with mutations in <jats:italic>BRAF<\/jats:italic>, <jats:italic>KRAS<\/jats:italic>, <jats:italic>MEK1<\/jats:italic> and <jats:italic>MEK2<\/jats:italic>. CFC has been considered a \u201csporadic\u201d disorder, with minimal recurrence risk to siblings. In recent years, vertical transmission of CFC has been seen in mutations involving the <jats:italic>MEK2<\/jats:italic> and <jats:italic>KRAS<\/jats:italic> genes, but has not previously been reported with <jats:italic>BRAF<\/jats:italic> mutations. Two brothers with clinical features of CFC and mutations in <jats:italic>BRAF<\/jats:italic> (c.770A\u2009&gt;\u2009G, p.Gln257Arg) are described. Neither parent (both phenotypically normal) had the <jats:italic>BRAF<\/jats:italic> mutation in their leukocyte DNA. Although this mutation is one of the most common mutations in CFC, to our knowledge, this is the first molecularly confirmed <jats:italic>BRAF<\/jats:italic> mutation causing CFC in siblings. This observation also likely represents the first description of germ cell mosaicism in CFC and so it is important to provide optimal genetic counselling to families regarding the risk of reoccurrence.<\/jats:p>","DOI":"10.1002\/ajmg.a.38725","type":"journal-article","created":{"date-parts":[[2018,4,28]],"date-time":"2018-04-28T07:35:59Z","timestamp":1524900959000},"page":"1637-1640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A sibling pair with cardiofaciocutaneous syndrome (CFC) secondary to <i>BRAF<\/i> mutation with unaffected parents\u2014the first cases of gonadal mosaicism in CFC?"],"prefix":"10.1002","volume":"176","author":[{"given":"Sarah","family":"Geoghegan","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Child Health Cork University Hospital Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2894-9360","authenticated-orcid":false,"given":"Graham","family":"King","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health Cork University Hospital Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Henchliffe","sequence":"additional","affiliation":[{"name":"St. Mary's Hospital, Manchester Academic Health Science Centre Manchester Centre for Genomic Medicine Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon C.","family":"Ramsden","sequence":"additional","affiliation":[{"name":"St. Mary's Hospital, Manchester Academic Health Science Centre Manchester Centre for Genomic Medicine Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond J.","family":"Barry","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health Mercy University Hospital Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Our Lady's Hospital Crumlin, School of Medicine and Medical Science University College Dublin Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M.","family":"O'Connell","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health Cork University Hospital Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.054460"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.2.161"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320410118"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31078"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34150"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0803-6"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200911"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1749"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-3189"},{"volume-title":"GeneReviews\u00ae","year":"2016","author":"Rauen K. A.","key":"e_1_2_6_11_1"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33342"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320250303"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124642"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32639"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01754.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng772"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2009.04.001"}],"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.38725","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38725","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.38725","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38725","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T04:39:22Z","timestamp":1694407162000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,28]]},"references-count":17,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1002\/ajmg.a.38725"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38725","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2018,4,28]]},"assertion":[{"value":"2017-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}