ArticleActa neuropathologica communications2017
Cryptic amyloidogenic elements in mutant NEFH causing Charcot-Marie-Tooth 2 trigger aggresome formation and neuronal death.
Article in Acta neuropathologica communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The genetic architecture of brainstem structures.Nature communications · 2025Pooled it
- Genetic commonalities between rare subtypes of ALS and CMT: insights into molecular mechanisms of neurodegeneration.Amino acids · 2026Review
- 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
- Diagnostic Challenges of Neuromuscular Disorders after Whole Exome Sequencing.Journal of neuromuscular diseases · 2023Article
- Neurofilaments in health and Charcot-Marie-Tooth disease.Frontiers in cell and developmental biology · 2023Review
- Severe congenital myasthenic syndromes caused by agrin mutations affecting secretion by motoneurons.Acta neuropathologica · 2022Article
- Epilepsy Combined With Multiple Gene Heterozygous Mutation.Frontiers in pediatrics · 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
- First case report of Charcot-Marie-Tooth disease type 2CC with a frameshift mutation of NEFH gene in Greece.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 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
- Article
- Neurofilaments: neurobiological foundations for biomarker applications.Brain : a journal of neurology · 2020Review
- Whole exome sequencing reveals a broader variant spectrum of Charcot-Marie-Tooth disease type 2.Neurogenetics · 2020Article
- Overlapping spectrums: The clinicogenetic commonalities between Charcot-Marie-Tooth and other neurodegenerative diseases.Brain research · 2020Review
- Anterograde Axonal Transport in Neuronal Homeostasis and Disease.Frontiers in molecular neuroscience · 2020Review
- A Systematic Review of Suggested Molecular Strata, Biomarkers and Their Tissue Sources in ALS.Frontiers in neurology · 2019Review
- The Peripheral Nervous System in Amyotrophic Lateral Sclerosis: Opportunities for Translational Research.Frontiers in neuroscience · 2019Review
- Defects in Axonal Transport in Inherited Neuropathies.Journal of neuromuscular diseases · 2019Review
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15 authors.
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Abstract
Neurofilament heavy chain (NEFH) gene was recently identified to cause autosomal dominant axonal Charcot-Marie-Tooth disease (CMT2cc). However, the clinical spectrum of this condition and the physio-pathological pathway remain to be delineated. We report 12 patients from two French families with axonal dominantly inherited form of CMT caused by two new mutations in the NEFH gene. A remarkable feature was the early involvement of proximal muscles of the lower limbs associated with pyramidal signs in some patients. Nerve conduction velocity studies indicated a predominantly motor axonal neuropathy. Unique deletions of two nucleotides causing frameshifts near the end of the NEFH coding sequence were identified: in family 1, c.3008_3009del (p.Lys1003Argfs*59), and in family 2 c.3043_3044del (p.Lys1015Glyfs*47). Both frameshifts lead to 40 additional amino acids translation encoding a cryptic amyloidogenic element. Consistently, we show that these mutations cause protein aggregation which are recognised by the autophagic pathway in motoneurons and triggered caspase 3 activation leading to apoptosis in neuroblastoma cells. Using electroporation of chick embryo spinal cord, we confirm that NEFH mutants form aggregates in vivo and trigger apoptosis of spinal cord neurons. Thus, our results provide a physiological explanation for the overlap between CMT and amyotrophic lateral sclerosis (ALS) clinical features in affected patients.
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