{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:33:28Z","timestamp":1769060008583,"version":"3.49.0"},"reference-count":27,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2017]]},"abstract":"<b><i>Background\/Aims:<\/i><\/b> To elucidate the genetic causes of severe primary insulin-like growth factor-I deficiency (SPIGFD) by systematic, targeted, next-generation sequencing (NGS)-based resequencing of growth-related genes. <b><i>Methods:<\/i><\/b> Clinical phenotyping followed by NGS in 17 families including 6 affected sib pairs. <b><i>Results:<\/i><\/b> We identified disease-causing, heterozygous, de novo variants in <i>HRAS<\/i> (p.Gly13Cys) and <i>FAM111A<\/i> (p.Arg569His) in 2 male patients with syndromic SPIGFD. A previously described homozygous <i>GHR<\/i> nonsense variant was detected in 2 siblings of a consanguineous family (p.Glu198*). Furthermore, we identified an inherited novel variant in the <i>IGF2<\/i> gene (p.Arg156Cys) of a maternally imprinted gene in a less severely affected father and his affected daughter. We detected 2 other novel missense variants in <i>SH2B1<\/i> and <i>SOCS2,<\/i> both were inherited from an unaffected parent. <b><i>Conclusions:<\/i><\/b> Screening of growth-related genes using NGS-based, large-scale, targeted resequencing identified disease-causing variants in <i>HRAS, FAM111A<\/i>, and <i>GHR<\/i>. Considering the increased risk of subjects with <i>HRAS<\/i> mutations for neoplasms, close clinical monitoring and a thorough discussion of the risk\/benefit ratio of the treatment with recombinant IGF-I is mandatory. Segregation analysis proved to be critical in the interpretation of potential SPIGFD-associated gene variations.<\/jats:p>","DOI":"10.1159\/000480505","type":"journal-article","created":{"date-parts":[[2017,10,26]],"date-time":"2017-10-26T21:01:24Z","timestamp":1509051684000},"page":"408-417","source":"Crossref","is-referenced-by-count":13,"title":["Targeted Resequencing of Putative Growth-Related Genes Using Whole Exome Sequencing in Patients with Severe Primary IGF-I Deficiency"],"prefix":"10.1159","volume":"88","author":[{"given":"Greta","family":"Grosse","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Hilger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heiko","family":"Reutter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franziska","family":"Lorenzen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gertrud","family":"Even","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul-Martin","family":"Holterhus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Woelfle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"German GHI Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2017,10,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1159\/000185018"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-014-0039-7"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9975"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1159\/000342548"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2006.11.004"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201506106"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1159\/000355928"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33884"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0810-575"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp528"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046688"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1159\/000360857"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2022"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.200"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038\/ng0593-98"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36444"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-14-0541"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1007\/BF03345551"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0995"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119803109"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1415227"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1021\/bi00699a002"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/480505","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/480505","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:55:02Z","timestamp":1745427302000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000480505"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":27,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,12,12]]}},"URL":"https:\/\/doi.org\/10.1159\/000480505","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.5519095","asserted-by":"subject"}]},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"value":"1663-2818","type":"print"},{"value":"1663-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]}}}