{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:24:09Z","timestamp":1790627049387,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,13]],"date-time":"2021-06-13T00:00:00Z","timestamp":1623542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Complete deletion of the NF1 gene is identified in 5\u201310% of patients with neurofibromatosis type 1 (NF1). Several studies have previously described particularly severe forms of the disease in NF1 patients with deletion of the NF1 locus, but comprehensive descriptions of large cohorts are still missing to fully characterize this contiguous gene syndrome. NF1-deleted patients were enrolled and phenotypically characterized with a standardized questionnaire between 2005 and 2020 from a large French NF1 cohort. Statistical analyses for main NF1-associated symptoms were performed versus an NF1 reference population. A deletion of the NF1 gene was detected in 4% (139\/3479) of molecularly confirmed NF1 index cases. The median age of the group at clinical investigations was 21 years old. A comprehensive clinical assessment showed that 93% (116\/126) of NF1-deleted patients fulfilled the NIH criteria for NF1. More than half had caf\u00e9-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described \u201cclassic\u201d NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients.<\/jats:p>","DOI":"10.3390\/cancers13122963","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T10:30:25Z","timestamp":1623666625000},"page":"2963","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Severe Phenotype in Patients with Large Deletions of NF1"],"prefix":"10.3390","volume":"13","author":[{"given":"Laurence","family":"Pacot","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP, Centre-Universit\u00e9 de Paris, F-75014 Paris, France"},{"name":"Inserm U1016\u2014CNRS UMR8104, Institut Cochin, Universit\u00e9 de Paris, CARPEM, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Vidaud","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP, Centre-Universit\u00e9 de Paris, F-75014 Paris, France"},{"name":"Inserm U1016\u2014CNRS UMR8104, Institut Cochin, Universit\u00e9 de Paris, CARPEM, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Sabbagh","sequence":"additional","affiliation":[{"name":"UMR 261, Laboratoire MERIT, IRD, Facult\u00e9 de Pharmacie de Paris, Universit\u00e9 de Paris, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Laurendeau","sequence":"additional","affiliation":[{"name":"Inserm U1016\u2014CNRS UMR8104, Institut Cochin, Universit\u00e9 de Paris, CARPEM, F-75014 Paris, 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H\u00f4pitaux Universitaires de Strasbourg, F-67000 Strasbourg, France"},{"name":"Medical Genetics Laboratory, INSERM U1112, Institute of Medical Genetics of Alsace, Strasbourg Medical School, University of Strasbourg, F-67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Guerrot","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique, CHU de Rouen, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Lespinasse","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique, CH de Chamb\u00e9ry, F-73000 Chamb\u00e9ry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Julia","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU de Toulouse, H\u00f4pital Purpan, F-31000 Toulouse, 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