{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:38:19Z","timestamp":1791041899290,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>RASopathies are a group of disorders caused by disruptions to the RAS\u2012MAPK pathway. Despite being in the same pathway, Neurofibromatosis Type 1 (NF1) and Legius syndrome (LS) typically present with phenotypes distinct from Noonan spectrum disorders (NSDs). However, some NF1\/LS individuals also exhibit NSD phenotypes, often referred to as Neurofibromatosis\u2010Noonan syndrome (NFNS), and may be mistakenly evaluated for NSDs, delaying diagnosis, and affecting patient management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A derivation cohort of 28 patients with a prior negative NSD panel and either NFNS or a suspicion of NSD and caf\u00e9\u2010au\u2010lait spots underwent\n                      <jats:italic>NF1<\/jats:italic>\n                      and\n                      <jats:italic>SPRED1<\/jats:italic>\n                      sequencing. To further determine the utility and burden of adding these genes, a validation cohort of 505 patients with a suspected RASopathy were tested on a 14\u2010gene RASopathy\u2010associated panel.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the derivation cohort, six (21%) patients had disease\u2010causing\n                      <jats:italic>NF1<\/jats:italic>\n                      or\n                      <jats:italic>SPRED1<\/jats:italic>\n                      variants. In the validation cohort, 11 (2%) patients had disease\u2010causing variants and 15 (3%) had variants of uncertain significance in\n                      <jats:italic>NF1<\/jats:italic>\n                      or\n                      <jats:italic>SPRED1<\/jats:italic>\n                      . Of those with disease\u2010causing variants, 5\/17 only had an NSD diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Adding\n                      <jats:italic>NF1<\/jats:italic>\n                      and\n                      <jats:italic>SPRED1<\/jats:italic>\n                      to RASopathy panels can speed diagnosis and improve patient management, without significantly increasing the burden of inconclusive results.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.1180","type":"journal-article","created":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T08:44:20Z","timestamp":1582879460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Expanding the Noonan spectrum\/RASopathy NGS panel: Benefits of adding\n                    <i>NF1<\/i>\n                    and\n                    <i>SPRED1<\/i>"],"prefix":"10.1002","volume":"8","author":[{"given":"Leora","family":"Witkowski","sequence":"first","affiliation":[{"name":"Departments of Pathology Harvard Medical School and Brigham and Women's Hospital Boston MA USA"},{"name":"Laboratory for Molecular Medicine Partners HealthCare Personalized Medicine Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6671-2252","authenticated-orcid":false,"given":"Mitchell W.","family":"Dillon","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Medicine Partners HealthCare Personalized Medicine Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elissa","family":"Murphy","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Medicine Partners HealthCare Personalized Medicine Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9733-5207","authenticated-orcid":false,"given":"Matthew","family":"S Lebo","sequence":"additional","affiliation":[{"name":"Departments of Pathology Harvard Medical School and Brigham and Women's Hospital Boston MA USA"},{"name":"Laboratory for Molecular Medicine Partners HealthCare Personalized Medicine Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0146-4881","authenticated-orcid":false,"given":"Heather","family":"Mason\u2010Suares","sequence":"additional","affiliation":[{"name":"Departments of Pathology Harvard Medical School and Brigham and Women's Hospital Boston MA USA"},{"name":"Laboratory for Molecular Medicine Partners HealthCare Personalized Medicine Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22152"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431\u2010011\u20101418\u20105"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu038"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23535"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.187"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1324128111"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e3283557231"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.4675"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23624"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010018\u20100269\u20100"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010018\u20100062\u20100"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096\u20108628(20001113)95:2<108:AID\u2010AJMG4>3.0.CO;2\u20100"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1560"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.156"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.204"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2010.05790.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32434"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098\u20101004(1996)8:1<51:AID\u2010HUMU7>3.0.CO;2\u2010S"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181d6f7c0"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.1180","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1180","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1180","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:21:15Z","timestamp":1780914075000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,27]]},"references-count":22,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1002\/mgg3.1180"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1180","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,27]]},"assertion":[{"value":"2019-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1180"}}