{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:03:38Z","timestamp":1789679018908,"version":"4.0.1"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T00:00:00Z","timestamp":1202083200000},"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":[[2008,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Costello syndrome is a rare congenital disorder typically characterized by severe failure\u2010to\u2010thrive, cardiac abnormalities including tachyarrhythmia and hypertrophic cardiomyopathy, distinctive facial features, a predisposition to papillomata and malignant tumors, neurologic abnormalities, developmental delay, and mental retardation. Its underlying cause is de novo germline mutations in the oncogene\n                    <jats:italic>HRAS<\/jats:italic>\n                    . Almost all Costello syndrome mutations affect one of the glycine residues in position 12 or 13 of the protein product. More than 80% of patients with Costello syndrome share the same underlying mutation, resulting in a G12S amino acid change. We report on two patients with novel\n                    <jats:italic>HRAS<\/jats:italic>\n                    mutations affecting amino acids 58 (T58I) and 146 (A146V), respectively. Despite facial features that appear less coarse than those typically seen in Costello patients, both patients show many of the physical and developmental problems characteristic for Costello syndrome. These novel\n                    <jats:italic>HRAS<\/jats:italic>\n                    mutations may be less common than the frequently reported G12S change, or patients with these changes may be undiagnosed due to their less coarse facial features. In addition to the findings previously known to occur in Costello syndrome, one of our patients had hypertrophic pyloric stenosis. This led us to review the medical histories on a cohort of proven\n                    <jats:italic>HRAS<\/jats:italic>\n                    mutation positive Costello syndrome patients, and we found a statistically significantly (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) increased frequency of pyloric stenosis in Costello syndrome (5\/58) compared to the general population frequency of 2\u20133\/1,000. Thus we add hypertrophic pyloric stenosis to the abnormalities seen with increased frequency in Costello syndrome. \u00a9 2008 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.32227","type":"journal-article","created":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T18:16:35Z","timestamp":1202148995000},"page":"683-690","source":"Crossref","is-referenced-by-count":66,"title":["Costello syndrome associated with novel germline\n                    <i>HRAS<\/i>\n                    mutations: An attenuated phenotype?"],"prefix":"10.1002","volume":"146A","author":[{"given":"Karen W.","family":"Gripp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Micheil","family":"Innes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marni E.","family":"Axelrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya L.","family":"Gillan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian S.","family":"Parboosingh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma J.","family":"Leonard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Lapointe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Doyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Catalano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Nicholson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah L.","family":"Stabley","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":[[2008,2,4]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1641"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30140"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31968"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31078"},{"key":"e_1_2_5_6_1","unstructured":"GrippK LinA.2006.Costello Syndrome in: GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Seattle: Copyright University of Washington. 1997\u20102006. Available athttp:\/\/www.genetests.org."},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31456"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31047"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(98)70284-7"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.040352"},{"key":"e_1_2_5_11_1","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1002\/j.1460-2075.1990.tb07409.x","article-title":"Refined crystal structure of the triphosphate conformation of H\u2010ras p21 at 1.35 A resolution: Implications for the mechanism of GTP hydrolysis","volume":"8","author":"Pai EF","year":"1990","journal-title":"EMBO J"},{"key":"e_1_2_5_12_1","unstructured":"Sanger Institute: Catalogue of Somatic Mutations in Cancer.2007.Distribution of somatic mutations in HRAS.www.sanger.ac.uk."},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1748"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20381"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.159.6.520"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2006.00474.x"},{"key":"e_1_2_5_17_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.32227","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.32227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T04:21:11Z","timestamp":1697602871000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.32227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,4]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2008,3,15]]}},"alternative-id":["10.1002\/ajmg.a.32227"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.32227","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2,4]]}}}