{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:27:18Z","timestamp":1767626838203},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,9]],"date-time":"2012-04-09T00:00:00Z","timestamp":1333929600000},"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":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Costello syndrome was delineated based on its distinctive phenotype 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> cause Costello syndrome, and its inheritance pattern would thus be autosomal dominant. With exception of two instances of parental mosaicism, one presumed gonadal and the other proven somatic mosaicism for the p.G12S change, all published cases resulted from de novo mutations, typically arising in the paternal germline. More than 90% of these mutations affect the glycine residues in position 12 or 13, and result in a gain\u2010of\u2010function of the altered protein. A rare heterozygous HRAS alteration (c.173C\u2009&gt;\u2009T; p.T58I) associated with an attenuated phenotype was previously reported in one patient. We identified two additional individuals with this mutation, father and son. Further studies supported origin of the alteration in the grand\u2010paternal germline. Transmission of the mutation underscores its attenuated phenotype compatible with reproduction. We reviewed the phenotype in the newly identified individuals (Patient 1, 2) and include updated information on the first previously reported individual with HRAS p.T58I (Patient 3). Macrocephaly was present in all three. Cardiac findings included hypertrophic cardiomyopathy with double\u2010chambered right ventricle; or mitral valve prolapse in one patient each. While subtle neurologic abnormalities or developmental delay were present in all, only one showed significant cognitive and functional impairment. None developed papillomata or a malignant tumor. Genetic counseling for Costello syndrome needs to take into consideration the particular <jats:italic>HRAS<\/jats:italic> mutation. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35294","type":"journal-article","created":{"date-parts":[[2012,4,9]],"date-time":"2012-04-09T20:13:19Z","timestamp":1334002399000},"page":"1095-1101","source":"Crossref","is-referenced-by-count":18,"title":["Transmission of the rare <i>HRAS<\/i> mutation (c. 173C\u2009&gt;\u2009T; p.T58I) further illustrates its attenuated phenotype"],"prefix":"10.1002","volume":"158A","author":[{"given":"Karen W.","family":"Gripp","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Hopkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norma J.","family":"Leonard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah L.","family":"Stabley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Sol\u2010Church","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,4,9]]},"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.33126"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.425"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.470"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp548"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21377"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32227"},{"key":"e_1_2_6_9_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_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33391"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.0b013e31822dd91f"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33884"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34150"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33857"},{"key":"e_1_2_6_15_1","article-title":"Assessing Genotype\u2010Phenotype correlation in Costello syndrome using a severity score","author":"McCormick E","year":"2012","journal-title":"Am J Med Genet"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-200107000-00004"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1748"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20381"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32639"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20100004.2011.01754.x"},{"key":"e_1_2_6_21_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.35294","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.35294","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:25:24Z","timestamp":1698711924000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.35294"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,9]]},"references-count":20,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.1002\/ajmg.a.35294"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.35294","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4,9]]}}}