Severe Phenotype in Patients with Large Deletions of NF1.
Laurence PacotDominique VidaudAudrey SabbaghIngrid LaurendeauAudrey Briand-SuleauAudrey CoustierThéodora MaillardCécile BarbanceFanny Morice-PicardSabine SigaudyOlga O GlazunovaLena DamajValérie LayetChloé QuelinBrigitte Gilbert-DussardierFrédérique AudicHélène DollfusAnne-Marie GuerrotJames LespinasseSophie JuliaMarie-Christine VantyghemMagali DrouardMarilyn LackmyBruno LeheupYves AlembikAlexia LemairePatrick NitschkéFlorence PetitAnne Dieux CoeslierEugénie MutezAlain TaiebMélanie FradinYline CapriHala NasserLyse RuaudBenjamin DauriatSylvie BourthoumieuDavid GenevièveSéverine Audebert-BellangerMathilde NizonRadka StoevaGeoffroy HickmanGaël NicolasJuliette Mazereeuw-HautierArnaud JannicSalah FerkalBéatrice ParfaitMichel Vidaudnull Members Of The Nf France NetworkPierre WolkensteinÉric PasmantPublished in: Cancers (2021)
Complete deletion of the NF1 gene is identified in 5-10% 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 café-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described "classic" 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.
Keyphrases
- signaling pathway
- lps induced
- pi k akt
- nuclear factor
- oxidative stress
- newly diagnosed
- inflammatory response
- ejection fraction
- cognitive impairment
- early onset
- gene expression
- depressive symptoms
- immune response
- gold nanoparticles
- genome wide
- cell proliferation
- cross sectional
- toll like receptor
- sleep quality
- spinal cord injury
- case report
- quantum dots