{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:56:03Z","timestamp":1790571363847,"version":"4.1.0"},"reference-count":9,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"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":["Pediatric Dermatology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Molecular confirmation of neurofibromatosis type 1 (NF1) is essential for accurate diagnosis, reproductive counseling, and lifelong surveillance, yet genomic DNA (gDNA)\u2010based next\u2010generation sequencing (NGS) panels may miss deep intronic or complex structural variants. We report five children meeting the 2021 NF1 clinical diagnostic criteria who had negative DNA\u2010based NGS testing but were subsequently diagnosed using\n NF1<\/jats:italic>\n cDNA\u2010based testing (\n NF1<\/jats:italic>\n cDNA testing), which identified three deep intronic variants, one 5\u2032UTR variant, and one exonic insertion, including three novel variants. Four of the five variants produced abnormal\u2010to\u2010normal transcript ratios of approximately 1:1, consistent with complete loss of normal transcript from the affected allele. These variants, detected by\u00a0\n NF1<\/jats:italic>\n cDNA testing, are predicted to result in the same clinical phenotype and natural history as\n NF1<\/jats:italic>\n exonic variants, underscoring the value of\n NF1<\/jats:italic>\n cDNA testing as a second\u2010tier test when clinical suspicion remains high despite negative gDNA\u2010based tests.\n <\/jats:p>","DOI":"10.1111\/pde.70257","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T08:57:54Z","timestamp":1778662674000},"page":"1170-1173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bridging the Diagnostic Gap in Neurofibromatosis Type 1: When to Consider\n \n NF1<\/i>\n cDNA\n <\/scp>\n Sequencing"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9497-0504","authenticated-orcid":false,"given":"Brent J.","family":"Doolan","sequence":"first","affiliation":[{"name":"Division of Dermatology the Hospital for Sick Children Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3078-1146","authenticated-orcid":false,"given":"Minu J.","family":"Chiramel","sequence":"additional","affiliation":[{"name":"Division of Dermatology the Hospital for Sick Children Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitch","family":"Hendry","sequence":"additional","affiliation":[{"name":"Division of Dermatology the Hospital for Sick Children Toronto Ontario Canada"},{"name":"Division of Clinical and Metabolic Genetics the Hospital for Sick Children Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Shugar","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics the Hospital for Sick Children Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9525-6081","authenticated-orcid":false,"given":"Yunjia","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical Genomics Laboratory, Department of Genetics University of Alabama at Birmingham Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3210-3413","authenticated-orcid":false,"given":"Irene","family":"Lara\u2010Corrales","sequence":"additional","affiliation":[{"name":"Division of Dermatology the Hospital for Sick Children Toronto Ontario Canada"},{"name":"Department of Paediatrics University of Toronto Toronto Ontario Canada"},{"name":"Child Health Evaluative Sciences, Peter Gilgan Centre for Research and Learning, the Hospital for Sick Children Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8031-6184","authenticated-orcid":false,"given":"Yiming","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics the Hospital for Sick Children Toronto Ontario Canada"},{"name":"Department of Paediatrics University of Toronto Toronto Ontario Canada"},{"name":"Genetics & Genome Biology Program, Peter Gilgan Centre for Research and Learning, the Hospital for Sick Children Toronto Ontario Canada"},{"name":"Institute of Medical Science, University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Neurofibromatosis 1","author":"Friedman J. 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