ArticleEBioMedicine2016
Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only.
Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 89 citations in OpenAlex.
- Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA).Molecular autism · 2018Trial
- Cancer risk in adults with pathogenic germline variants in RAS/MAPK genes using genomic ascertainment.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Genetic and non-genetic factors influencing phenotypic variability in neurofibromatosis type 1.Orphanet journal of rare diseases · 2026Review
- PKD1 5'UTR variants are a rare cause of disease in ADPKD and suggest a new focus for therapeutic development.European journal of human genetics : EJHG · 2026Article
- Reassessment of variants of uncertain significance in tumor suppressor genes using new ClinGen PP1/PP4 criteria guidance.European journal of human genetics : EJHG · 2025Article
- The role of untranslated region variants in Mendelian disease: a review.European journal of human genetics : EJHG · 2025Review
- A Comprehensive Overview of NF1 Mutations in Iranian Patients.Neuromolecular medicine · 2024Article
- Diagnosis and management of neurofibromatosis type 1 in Arabian Gulf Cooperation Council Region: challenges and recommendations.Frontiers in oncology · 2024Review
- Mutation analysis and clinical profile of South African patients with Neurofibromatosis type 1 (NF1) phenotype.Frontiers in genetics · 2024Article
- Deep Intronic LINE-1 Insertions inBiomolecules · 2023Article
- VIsoQLR: an interactive tool for the detection, quantification and fine-tuning of isoforms in selected genes using long-read sequencing.Human genetics · 2023Article
- High-yield identification of pathogenic NF1 variants by skin fibroblast transcriptome screening after apparently normal diagnostic DNA testing.Human mutation · 2022Article
- Case series of congenital pseudarthrosis of the tibia unfulfilling neurofibromatosis type 1 diagnosis: 21% with somatic NF1 haploinsufficiency in the periosteum.Human genetics · 2022Article
- Recommendations for clinical interpretation of variants found in non-coding regions of the genome.Genome medicine · 2022Article
- Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and RecurrentGenes · 2022Article
- Review
- Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1.Molecular genetics & genomic medicine · 2021Article
- Pathogenic neurofibromatosis type 1 (NF1) RNA splicing resolved by targeted RNAseq.NPJ genomic medicine · 2021Article
- Article
- Cutaneous Findings in Neurofibromatosis Type 1.Cancers · 2021Review
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe detection rate for identifying the underlying mutation in neurocutaneous syndromes is affected by the sensitivity of the mutation test and the heterogeneity of the disease based on the diagnostic criteria. Neurofibromatosis type (NF1) has been defined for 29years by the National Institutes for Health (NIH) criteria which include ≥6 Café au Lait macules (CAL) as a defining criterion. The discovery of SPRED1 as a cause of Legius syndrome which is manifested by CAL, freckling and learning difficulties has introduced substantial heterogeneity to the NIH criteria.
methodsWe have defined the sensitivity of comprehensive RNA analysis on blood of presumed NF1 patients meeting NIH criteria with at least one nonpigmentary criterion and determined the proportion of children with ≥6 CAL and no family history that has an NF1 or SPRED1 genetic variant. RNA analysis was carried out from 04/2009-12/2015 on 361 NF1 patients.
findingsA presumed causative NF1 mutation was found in 166/171 (97.08%-95% CI 94.56-99.6%) of familial cases and 182/190 (95.8%-95% CI 92.93-98.65%) sporadic de novo cases. Two of thirteen (15%) mutation negative individuals had dysembryoplastic neuroepithelial tumour (DNET) compared to 2/348 (0.6%) with an NF1 variant (p=0.007). No SPRED1 variants were found in the thirteen individuals with no NF1 variant. Of seventy-one individuals with ≥6 CAL and no non-pigmentary criterion aged 0-20years, 47 (66.2%) had an NF1 variant six (8.5%) a SPRED1 variant and 18 (25.3%) no disease causing variant. Using the 95.8% detection rate the likelihood of a child with ≥6 CAL having constitutional NF1 drops from 2/3 to 1/9 after negative RNA analysis.
interpretationRNA analysis in individuals with presumed NF1 has high sensitivity and includes a small subset with DNET without an NF1 variant. Furthermore negative analysis for NF1/SPRED1 provides strong reassurance to children with ≥6 CAL that they are unlikely to have NF1.
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