{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:30:58Z","timestamp":1773145858778,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2010,7,2]],"date-time":"2010-07-02T00:00:00Z","timestamp":1278028800000},"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":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Caf\u00e9\u2010au\u2010lait macules are frequently seen in Ras\u2010MAPK pathway disorders and are a cardinal feature of neurofibromatosis type 1 (NF1). Most NF1 individuals develop age\u2010related tumorigenic manifestations (e.g., neurofibromas), although individuals with a specific 3\u2010bp deletion in exon 22 of <jats:italic>NF1<\/jats:italic> (c.2970_2972delAAT) have an attenuated phenotype with primarily pigmentary manifestations. Previous reports identify this deletion c.2970_2972delAAT in exon 17 of <jats:italic>NF1<\/jats:italic> using NF Consortium nomenclature. For this report, we elected to use standard NCBI nomenclature, which places this identical deletion within exon 22. <jats:italic>SPRED1<\/jats:italic> mutations cause Legius syndrome, which clinically overlaps with this attenuated NF1 phenotype. In an unselected cohort of 50 individuals who fulfilled NIH clinical diagnostic criteria from an NF Clinic and did not have <jats:italic>SPRED1<\/jats:italic> mutations, we sequenced <jats:italic>NF1<\/jats:italic> exon 22 in order to identify children and adolescents with multiple caf\u00e9\u2010au\u2010lait spots who could be projected to have lower likelihood to develop tumors. Two individuals with <jats:italic>NF1<\/jats:italic> exon 22 mutations were identified: an 11\u2010year\u2010old boy with the c.2970_2972delAAT in\u2010frame deletion and a 4\u2010year\u2010old boy with c.2866dupA. The father of the second patient had an attenuated form of NF1 and showed 24% germline mosaicism of the c.2866dupA mutation in whole blood. These individuals emphasize the need for mutation analysis in some individuals with the clinical diagnosis of NF1 who lack the tumorigenic or classic skeletal abnormalities of NF1. Specifically, with the identification of Legius syndrome, the need to recognize the attenuated phenotype of <jats:italic>NF1<\/jats:italic> mosaicism and confirmation by mutation analysis is increasingly important for appropriate medical management and family counseling. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33525","type":"journal-article","created":{"date-parts":[[2010,7,6]],"date-time":"2010-07-06T22:25:07Z","timestamp":1278455107000},"page":"1973-1978","source":"Crossref","is-referenced-by-count":11,"title":["NF1 exon 22 analysis of individuals with the clinical diagnosis of neurofibromatosis type 1"],"prefix":"10.1002","volume":"152A","author":[{"given":"Talia M.","family":"Muram\u2010Zborovski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecily P.","family":"Vaughn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Viskochil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Hanson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,7,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.6.e82"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2113"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23834.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970516)70:2<138::AID-AJMG7>3.0.CO;2-U"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/423624"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199411243312102"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/519562"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1663"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073809359540"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01233.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2008.01170.x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.065243"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.7.520"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.065474"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000126503"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00576.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/510781"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.2.102"}],"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.33525","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33525","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T20:07:27Z","timestamp":1696709247000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7,20]]},"references-count":19,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2010,8]]}},"alternative-id":["10.1002\/ajmg.a.33525"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33525","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,7,20]]}}}