ArticleAmerican journal of human genetics2016
Cryptic Amyloidogenic Elements in the 3' UTRs of Neurofilament Genes Trigger Axonal Neuropathy.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 59 citations in OpenAlex.
- "Missing mutations" in MPS I: Identification of two novel copy number variations by an IDUA-specific in house MLPA assay.Molecular genetics & genomic medicine · 2019Trial
- Article
- Massive mutagenesis reveals an incomplete amyloid motif in Bri2 that turns amyloidogenic upon C-terminal extension.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Charcot-Marie-Tooth type 2CC misdiagnosed as Chronic Inflammatory Demyelinating Polyradiculoneuropathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Suppressive cancer nonstop extension mutations increase C-terminal hydrophobicity and disrupt evolutionarily conserved amino acid patterns.Nature communications · 2024Article
- Neurofilament Biophysics: From Structure to Biomechanics.Molecular biology of the cell · 2024Review
- Neurofilaments as biomarkers in neurological disorders - towards clinical application.Nature reviews. Neurology · 2024Review
- Genetic characterization of non-5q proximal spinal muscular atrophy in a French cohort: the place of whole exome sequencing.European journal of human genetics : EJHG · 2024Article
- Article
- Posttranscriptional regulation of neurofilament proteins and tau in health and disease.Brain research bulletin · 2023Review
- Neurofilaments in health and Charcot-Marie-Tooth disease.Frontiers in cell and developmental biology · 2023Review
- The 2022 Lady Estelle Wolfson lectureship on neurofilaments.Journal of neurochemistry · 2022Review
- Neurons: The Interplay between Cytoskeleton, Ion Channels/Transporters and Mitochondria.Cells · 2022Review
- Clinical and Genetic Survey for Charcot-Marie-Tooth Neuropathy Based on the Findings in Turkey, a Country with a High Rate of Consanguineous MarriagesBalkan medical journal · 2022Article
- A novel single-point mutation of NEFH and biallelic SACS mutation presenting as intermediate form Charcot-Marie-Tooth: A case report in Vietnam.Surgical neurology international · 2022Article
- Charcot-Marie-Tooth disease type 2CC due toJournal of neurology, neurosurgery, and psychiatry · 2022Observational
- Epilepsy Combined With Multiple Gene Heterozygous Mutation.Frontiers in pediatrics · 2022Article
- Protein products of nonstop mRNA disrupt nucleolar homeostasis.Cell stress & chaperones · 2021Article
- A novel missense pathogenic variant in NEFH causing rare Charcot-Marie-Tooth neuropathy type 2CC.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Article
- A Chinese Patient with Spastic Paraplegia Type 4 with aCase reports in genetics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 3 countries.
Funding
Abstract
Abnormal protein aggregation is observed in an expanding number of neurodegenerative diseases. Here, we describe a mechanism for intracellular toxic protein aggregation induced by an unusual mutation event in families affected by axonal neuropathy. These families carry distinct frameshift variants in NEFH (neurofilament heavy), leading to a loss of the terminating codon and translation of the 3' UTR into an extra 40 amino acids. In silico aggregation prediction suggested the terminal 20 residues of the altered NEFH to be amyloidogenic, which we confirmed experimentally by serial deletion analysis. The presence of this amyloidogenic motif fused to NEFH caused prominent and toxic protein aggregates in transfected cells and disrupted motor neurons in zebrafish. We identified a similar aggregation-inducing mechanism in NEFL (neurofilament light) and FUS (fused in sarcoma), in which mutations are known to cause aggregation in Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis, respectively. In summary, we present a protein-aggregation-triggering mechanism that should be taken into consideration during the evaluation of stop-loss variants.
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.