ArticleHuman molecular genetics2015
Elucidating the impact of neurofibromatosis-1 germline mutations on neurofibromin function and dopamine-based learning.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.
What it found
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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
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Brain volumes in genetic syndromes associated with mTOR dysregulation: a systematic review and meta-analysis.Molecular psychiatry · 2025Pooled it
- Social Communication in Ras Pathway Disorders: A Comprehensive Review From Genetics to Behavior in Neurofibromatosis Type 1 and Noonan Syndrome.Biological psychiatry · 2025Pooled it
- Trial
- Relation Between Genotype and Behavioral Phenotype in Children and Adolescents With Neurofibromatosis Type 1.JAACAP open · 2026Article
- Gut microbiome alterations are sex-dependently associated with brain abnormalities in a mouse model of Neurofibromatosis type I.Molecular psychiatry · 2026Article
- Autism in neurofibromatosis type 1: prevalence, phenotype and clinical implications.Molecular autism · 2026Article
- Zebrafish neurofibromatosis type 1 mutants show disruption of sleep but not of circadian rhythms.Sleep · 2026Article
- Metabolic and behavioral effects of neurofibromin result from differential recruitment of MAPK and mTOR signaling.PLoS genetics · 2026Article
- Colon cancer in a patient with a mosaic monoallelic germline pathogenicExploration of neuroscience · 2026Article
- Article
- Current states in understanding oligodendroglia-mediated neurological issues in neurofibromatosis type 1 (NF1).Acta neuropathologica communications · 2025Review
- Cognition and behavior in neurofibromatosis type 1: report and perspective from the Cognition and Behavior in NF1 (CABIN) Task Force.Genes & development · 2025Article
- A scarce case: Co-occurrence of neurofibromatosis type 1 and Klinefelter syndrome.Global medical genetics · 2025Article
- Unraveling neuronal and metabolic alterations in neurofibromatosis type 1.Journal of neurodevelopmental disorders · 2024Review
- The genetic spectrum ofNeurosciences (Riyadh, Saudi Arabia) · 2024Article
- An Overview of Optic Pathway Glioma With Neurofibromatosis Type 1: Pathogenesis, Risk Factors, and Therapeutic Strategies.Investigative ophthalmology & visual science · 2024Review
- Review
- The therapeutic potential of neurofibromin signaling pathways and binding partners.Communications biology · 2023Review
- Article
- The efficacy of statins for improving cognitive impairments in pediatric patients with neurofibromatosis type 1 (NF-1): a meta-analysis.Frontiers in pediatrics · 2023Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Neurofibromatosis type 1 (NF1) is a common autosomal dominant neurologic condition characterized by significant clinical heterogeneity, ranging from malignant cancers to cognitive deficits. Recent studies have begun to reveal rare genotype-phenotype correlations, suggesting that the specific germline NF1 gene mutation may be one factor underlying disease heterogeneity. The purpose of this study was to define the impact of the germline NF1 gene mutation on brain neurofibromin function relevant to learning. Herein, we employ human NF1-patient primary skin fibroblasts, induced pluripotent stem cells and derivative neural progenitor cells (NPCs) to demonstrate that NF1 germline mutations have dramatic effects on neurofibromin expression. Moreover, while all NF1-patient NPCs exhibit increased RAS activation and reduced cyclic AMP generation, there was a neurofibromin dose-dependent reduction in dopamine (DA) levels. Additionally, we leveraged two complementary Nf1 genetically-engineered mouse strains in which hippocampal-based learning and memory is DA-dependent to establish that neuronal DA levels and signaling as well as mouse spatial learning are controlled in an Nf1 gene dose-dependent manner. Collectively, this is the first demonstration that different germline NF1 gene mutations differentially dictate neurofibromin function in the brain.
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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.