{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:24:10Z","timestamp":1790627050204,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,7,16]],"date-time":"2018-07-16T00:00:00Z","timestamp":1531699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurofibromatosis type I (NF1) is one of the most common genetic disorders in humans. NF1, a tumor predisposition syndrome, is caused by heterozygous pathogenic variants in the <jats:italic>NF1<\/jats:italic> gene. Molecular genetic testing of <jats:italic>NF1<\/jats:italic> is complex, especially because of the presence of a high number of partial pseudogenes, some of them with a high percentage of sequence identity.<\/jats:p><jats:p>In this study, we have analyzed the largest cohort of NF1 Spanish patients (150 unrelated individuals suspected of having NF1 and 53 relatives, making a total of 203 individuals). Mutation analysis of the entire coding region was performed in all unrelated index patients. Additionally, the Multiplex Ligation\u2010dependent Probe Amplification (MLPA) test of the <jats:italic>NF1<\/jats:italic> gene and <jats:italic>SPRED1<\/jats:italic> gene analysis (sequencing and MLPA test) was performed in some of the negative patients for <jats:italic>NF1<\/jats:italic> point mutations.<\/jats:p><jats:p>When fulfilling the National Institutes of Health (NIH) criterion for the clinical diagnosis of NF1, the detection rate was 79%. Among the 80 genetically confirmed NF1 probands, we detected 69 different pathogenic variants. Two mutations (3%) were gross deletions of the whole gene, the remaining 78 mutations (97%) were small changes spread among all <jats:italic>NF1<\/jats:italic> exons. Among these 69 different mutations detected, 42 mutations were described elsewhere, and 27 mutations were novel mutations. When segregation was studied, 67% of mutations resulted <jats:italic>de novo<\/jats:italic> variants. No genetic mosaicism was detected on patients\u2019 parents.<\/jats:p>","DOI":"10.1111\/ahg.12272","type":"journal-article","created":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T05:00:41Z","timestamp":1531803641000},"page":"425-436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Neurofibromatosis type I: mutation spectrum of <i>NF1<\/i> in spanish patients"],"prefix":"10.1111","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1718-4390","authenticated-orcid":false,"given":"Carmen","family":"Palma Milla","sequence":"first","affiliation":[{"name":"C.G.M Genetaq  M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Miguel","family":"Lezana Rosales","sequence":"additional","affiliation":[{"name":"C.G.M Genetaq  M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"L\u00f3pez Montiel","sequence":"additional","affiliation":[{"name":"C.G.M Genetaq  M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas David","family":"Andr\u00e9s Garrido","sequence":"additional","affiliation":[{"name":"C.G.M Genetaq  M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"S\u00e1nchez Linares","sequence":"additional","affiliation":[{"name":"C.G.M Genetaq  M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Carmona Tamaj\u00f3n","sequence":"additional","affiliation":[{"name":"C.G.M Genetaq  M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Torres Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"C.G.M Genetaq  M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"S\u00e1nchez Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"C.G.M Genetaq  M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Franco Freire","sequence":"additional","affiliation":[{"name":"Hospital Regional Universitario de M\u00e1laga. U.G.C. de Laboratorio. Secci\u00f3n de Gen\u00e9tica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Benito L\u00f3pez","sequence":"additional","affiliation":[{"name":"Hospital Regional Universitario de M\u00e1laga. U.G.C. de Laboratorio. Secci\u00f3n de Gen\u00e9tica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"L\u00f3pez Siles","sequence":"additional","affiliation":[{"name":"C.G.M Genetaq  M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380030404"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.2.237"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.6.e82"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.9.638"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.161"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.161"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.7.2632-2643.2005"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.055772"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp215"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33139"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/302809"},{"key":"e_1_2_8_13_1","volume-title":"Neurofibromatosis 1, GeneReviews(\u00ae)","author":"Friedman J.","year":"1993"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-006-9001-3"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.6.975"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000126500"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181bf15e3"},{"key":"e_1_2_8_18_1","first-page":"187","volume-title":"NF1 microdeletions and their underlying mutational mechanisms\u2019, in neurofibromatosis type 1","author":"Kehrer\u2010Sawatzki H.","year":"2012"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/msb.20145092"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10299"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2013.02.004"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.141.1.71"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1222"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-5-6-623"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9446"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl016"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.011890"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.075937"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050427"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.551"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-199909000-00002"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N"},{"issue":"3","key":"e_1_2_8_35_1","first-page":"172","volume":"1","author":"National Institutes of Health Consensus Development Conference Statement: Neurofibromatosis. Bethesda, Md., USA, July 13\u201315, 1987","year":"1988","journal-title":"Neurofibromatosis"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.10.813"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21271"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-100978"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.145"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1897-4287-9-6"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20826"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.01.002"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a010118"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00214193"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22392"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974-9233.148361"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1358-4"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.207"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.129"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1997)10:3<248::AID-HUMU14>3.0.CO;2-#"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20793"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.4.639"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050438"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12187"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fahg.12272","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12272","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ahg.12272","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T03:02:32Z","timestamp":1693364552000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.12272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,16]]},"references-count":55,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1111\/ahg.12272"],"URL":"https:\/\/doi.org\/10.1111\/ahg.12272","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,16]]},"assertion":[{"value":"2018-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}