ArticleHuman mutation2022
High-yield identification of pathogenic NF1 variants by skin fibroblast transcriptome screening after apparently normal diagnostic DNA testing.
Article in Human mutation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Relation Between Genotype and Behavioral Phenotype in Children and Adolescents With Neurofibromatosis Type 1.JAACAP open · 2026Article
- Genetic and non-genetic factors influencing phenotypic variability in neurofibromatosis type 1.Orphanet journal of rare diseases · 2026Review
- Report of Concomitant Intracranial Cysts in Unrelated Patients With Heterozygous GermlineAnnals of internal medicine. Clinical cases · 2026Article
- Protein domain-specific genotype-phenotype correlation study of neurofibromatosis type 1.Scientific reports · 2025Article
- Neurofibromatosis Type 1 : A General Review.Journal of Korean Neurosurgical Society · 2025Article
- Identification of technically challenging variants: Whole-genome sequencing improves diagnostic yield in patients with high clinical suspicion of rare diseases.HGG advances · 2025Article
- Beyond genomics: using RNA-seq from dried blood spots to unlock the clinical relevance of splicing variation in a diagnostic setting.European journal of human genetics : EJHG · 2025Article
- Molecular insights into genodermatoses: Genetic findings from 43 patients.Archives of dermatological research · 2025Article
- A novel synonymous variant in the NF1 gene disrupting splicing contributes to neurofibromatosis pathogenesis.Frontiers in genetics · 2025Article
- Facing the challenges to shorten the diagnostic odyssey: first Whole Genome Sequencing experience of a Colombian cohort with suspected rare diseases.European journal of human genetics : EJHG · 2024Article
- The Role of Fibroblasts in Skin Homeostasis and Repair.Biomedicines · 2024Review
- Deep Intronic LINE-1 Insertions inBiomolecules · 2023Article
- Web-accessible application for identifying pathogenic transcripts with RNA-seq: Increased sensitivity in diagnosis of neurodevelopmental disorders.American journal of human genetics · 2023Article
- Functional Assays Combined with Pre-mRNA-Splicing Analysis Improve Variant Classification and Diagnostics for Individuals with Neurofibromatosis Type 1 and Legius Syndrome.Human mutation · 2023Article
- High-yield identification of pathogenic NF1 variants by skin fibroblast transcriptome screening after apparently normal diagnostic DNA testing.Human mutation · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurofibromatosis type 1 (NF1) is caused by inactivating mutations in NF1. Due to the size, complexity, and high mutation rate at the NF1 locus, the identification of causative variants can be challenging. To obtain a molecular diagnosis in 15 individuals meeting diagnostic criteria for NF1, we performed transcriptome analysis (RNA-seq) on RNA obtained from cultured skin fibroblasts. In each case, routine molecular DNA diagnostics had failed to identify a disease-causing variant in NF1. A pathogenic variant or abnormal mRNA splicing was identified in 13 cases: 6 deep intronic variants and 2 transposon insertions causing noncanonical splicing, 3 postzygotic changes, 1 branch point mutation and, in 1 case, abnormal splicing for which the responsible DNA change remains to be identified. These findings helped resolve the molecular findings for an additional 17 individuals in multiple families with NF1, demonstrating the utility of skin-fibroblast-based transcriptome analysis for molecular diagnostics. RNA-seq improves mutation detection in NF1 and provides a powerful complementary approach to DNA-based methods. Importantly, our approach is applicable to other genetic disorders, particularly those caused by a wide variety of variants in a limited number of genes and specifically for individuals in whom routine molecular DNA diagnostics did not identify the causative variant.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.