{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T12:33:17Z","timestamp":1774787597521,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T00:00:00Z","timestamp":1401235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL071207"],"award-info":[{"award-number":["HL071207"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Telethon-Italy","award":["GGP13107"],"award-info":[{"award-number":["GGP13107"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>The RASopathies are a relatively common group of phenotypically similar and genetically related autosomal dominant genetic syndromes caused by missense mutations affecting genes participating in the RAS\/mitogen\u2010activated protein kinase (MAPK) pathway that include Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML, formerly LEOPARD syndrome). NS and NSML can be difficult to differentiate during infancy, but the presence of multiple lentigines, caf\u00e9 au lait spots, and specific cardiac defects facilitate the diagnosis. Furthermore, individual <jats:italic>PTPN11<\/jats:italic> missense mutations are highly specific to each syndrome and engender opposite biochemical alterations on the function of SHP\u20102, the protein product of that gene. Here, we report on a 5\u2010year\u2010old male with two de novo <jats:italic>PTPN11<\/jats:italic> mutations in <jats:italic>cis<\/jats:italic>, c.1471C&gt;T (p.Pro491Ser), and c.1492C&gt;T (p.Arg498Trp), which are associated with NS and NSML, respectively. This boy's phenotype is intermediate between NS and NSML with facial dysmorphism, short stature, mild global developmental delay, pulmonic stenosis, and deafness but absence of caf\u00e9 au lait spots or lentigines. The double\u2010mutant SHP\u20102 was found to be catalytically impaired. This raises the question of whether clinical differences between NS and NSML can be ascribed solely to the relative SHP\u20102 catalytic activity. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36620","type":"journal-article","created":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T18:56:23Z","timestamp":1401303383000},"page":"2351-2355","source":"Crossref","is-referenced-by-count":13,"title":["A <i>PTPN11<\/i> allele encoding a catalytically impaired SHP2 protein in a patient with a Noonan syndrome phenotype"],"prefix":"10.1002","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8153-7066","authenticated-orcid":false,"given":"Jonathan J.","family":"Edwards","sequence":"first","affiliation":[{"name":"Department of Pediatrics Icahn School of Medicine at Mount Sinai New York New York"},{"name":"Mindich Child Health and Development Institute Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Pannone","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan Fai\u2010Man","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Health Clinical Genetic Service Hong Kong SAR"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Edelmann","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ho\u2010Ming","family":"Luk","sequence":"additional","affiliation":[{"name":"Department of Health Clinical Genetic Service Hong Kong SAR"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce D.","family":"Gelb","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Icahn School of Medicine at Mount Sinai New York New York"},{"name":"Mindich Child Health and Development Institute Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,5,28]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1084"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31156"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000331266"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.143.9.1210"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20005"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.03.088"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0929-6646(09)60235-7"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513068200"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-005-0031-x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.05.024"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2009.08.021"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44972"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn099"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-091212-153523"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.013466"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-3-13"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2006.104547"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05790.x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/499925"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2010.09.002"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(76)90764-6"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.450023"}],"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.36620","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36620","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T14:46:14Z","timestamp":1700664374000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,28]]},"references-count":22,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1002\/ajmg.a.36620"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36620","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,28]]}}}