{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:15:43Z","timestamp":1790630143905,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,8,10]],"date-time":"2011-08-10T00:00:00Z","timestamp":1312934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Costello syndrome was first reported based on its characteristic phenotype. Its presentation affects multiple organ systems, including severe failure\u2010to\u2010thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. Heterozygous germline mutations in the proto\u2010oncogene <jats:italic>HRAS<\/jats:italic> have been recognized to cause Costello syndrome, and its inheritance pattern would thus be autosomal dominant. Here, we report on the identification of an <jats:italic>HRAS<\/jats:italic> mutation c.34G&gt;A, predicting a p.G12S amino acid substitution, in the surviving brother of a previously reported sibling pair, and documentation of the same change in autopsy material from his deceased sister. This represents, to our knowledge, the first molecularly confirmed Costello syndrome in siblings. We did not detect the mutation in a heterozygous state or mosaicism in peripheral white blood cell or cheek swab\u2010derived DNA samples from either parent. Using single nucleotide polymorphic markers and allele\u2010specific amplification, we clearly identified the mutation in the surviving sibling to be of maternal origin. While we cannot exclude two independently occurring de novo mutations, the complete sharing of polymorphic markers around the mutation site in both siblings supports maternal germ cell mosaicism. Recurrence risk counseling for families with apparently de novo occurring autosomal dominant conditions includes discussion of germ cell mosaicism, and this report underscores the applicability of this concern to Costello syndrome. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.34150","type":"journal-article","created":{"date-parts":[[2011,8,10]],"date-time":"2011-08-10T20:42:44Z","timestamp":1313008964000},"page":"2263-2268","source":"Crossref","is-referenced-by-count":23,"title":["Molecular confirmation of HRAS p.G12S in siblings with Costello syndrome"],"prefix":"10.1002","volume":"155","author":[{"given":"Karen W.","family":"Gripp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah L.","family":"Stabley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Geller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hopkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Carey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Sol\u2010Church","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,8,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1641"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33687"},{"key":"e_1_2_6_4_1","unstructured":"GrippK LinA.2009.Costello syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright University of Washington Seattle 1997\u20132009. Available at:http:\/\/www.genetests.org."},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31456"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33586"},{"key":"e_1_2_6_7_1","first-page":"353","article-title":"Costello syndrome in two siblings and minor manifestations in their mother, further evidence for autosomal dominant inheritance?","volume":"13","author":"Ioan DM","year":"2002","journal-title":"Genet Couns"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(98)70284-7"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20381"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32639"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.049361"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.333"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320470210"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20431"}],"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.34150","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.34150","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T17:52:45Z","timestamp":1697651565000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.34150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8,10]]},"references-count":13,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1002\/ajmg.a.34150"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.34150","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,8,10]]}}}