ArticleHuman molecular genetics2018
Homozygous mutation in the Neurofascin gene affecting the glial isoform of Neurofascin causes severe neurodevelopment disorder with hypotonia, amimia and areflexia.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 32 citations in OpenAlex.
- Transcriptomic Profiling of Zebrafish Mutant forInternational journal of molecular sciences · 2025Article
- Altered plasma membrane abundance of the sulfatide-binding protein NF155 links glycosphingolipid imbalances to demyelination.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The structure of sensory afferent compartments in health and disease.Journal of anatomy · 2022Review
- Multi-omic profiling reveals the ataxia protein sacsin is required for integrin trafficking and synaptic organization.Cell reports · 2022Article
- FINCA syndrome-Defining neurobehavioral phenotype in survivors into late childhood.Molecular genetics & genomic medicine · 2022Article
- Bi-allelic variants in neuronal cell adhesion molecule cause a neurodevelopmental disorder characterized by developmental delay, hypotonia, neuropathy/spasticity.American journal of human genetics · 2022Article
- Article
- Neurofascin antibodies in chronic inflammatory demyelinating polyradiculoneuropathy: from intrinsic genetic background to clinical manifestations.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Review
- iPSC-derived myelinoids to study myelin biology of humans.Developmental cell · 2021Article
- Identification of methylation changes associated with positive and negative growth deviance in Gambian infants using a targeted methyl sequencing approach of genomic DNA.FASEB bioAdvances · 2021Article
- Mechanisms of node of Ranvier assembly.Nature reviews. Neuroscience · 2021Review
- Deletion of the Thrombin Proteolytic Site in Neurofascin 155 Causes Disruption of Nodal and Paranodal Organization.Frontiers in cellular neuroscience · 2021Article
- Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit.Journal of clinical medicine · 2020Article
- AP4B1-associated hereditary spastic paraplegia: expansion of phenotypic spectrum related to homozygous p.Thr387fs variant.Journal of applied genetics · 2020Article
- Oligodendrocyte Neurofascin Independently Regulates Both Myelin Targeting and Sheath Growth in the CNS.Developmental cell · 2019Article
- Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination.Brain : a journal of neurology · 2019Article
- Ataxia in Patients With Bi-AllelicFrontiers in genetics · 2019Article
- Loss of Neurofascin-186 Disrupts Alignment of AnkyrinG Relative to Its Binding Partners in the Axon Initial Segment.Frontiers in cellular neuroscience · 2019Article
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17 authors at 3 institutions in 2 countries.
Funding
Abstract
The Neurofascins (NFASCs) are a family of proteins encoded by alternative transcripts of NFASC that cooperate in the assembly of the node of Ranvier in myelinated nerves. Differential expression of NFASC in neurons and glia presents a remarkable example of cell-type specific expression of protein isoforms with a common overall function. In mice there are three NFASC isoforms: Nfasc186 and Nfasc140, located in the axonal membrane at the node of Ranvier, and Nfasc155, a glial component of the paranodal axoglial junction. Nfasc186 and Nfasc155 are the major isoforms at mature nodes and paranodes, respectively. Conditional deletion of the glial isoform Nfasc155 in mice causes severe motor coordination defects and death at 16-17 days after birth. We describe a proband with severe congenital hypotonia, contractures of fingers and toes, and no reaction to touch or pain. Whole exome sequencing revealed a homozygous NFASC variant chr1:204953187-C>T (rs755160624). The variant creates a premature stop codon in 3 out of four NFASC human transcripts and is predicted to specifically eliminate Nfasc155 leaving neuronal Neurofascin intact. The selective absence of Nfasc155 and disruption of the paranodal junction was confirmed by an immunofluorescent study of skin biopsies from the patient versus control. We propose that the disease in our proband is the first reported example of genetic deficiency of glial Neurofascin isoforms in humans and that the severity of the condition reflects the importance of the Nfasc155 in forming paranodal axoglial junctions and in determining the structure and function of the node of Ranvier.
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