The first Portuguese family with NEFL-related Charcot-Marie-Tooth type 2 disease.

The first Portuguese family with NEFL-related Charcot-Marie-Tooth type 2 disease. Acta Myol. 2019 Sep;38(3):180-183 Authors: Machado R, Pinto-Basto J, Negrão L Abstract CMT disease caused by NEFL gene mutations is rare. The mode of inheritance can be dominant or recessive and nerve conduction velocities can be normal, reduced (demyelinating) or presenting intermediate values. Two Portuguese adult related members in two successive generations were affected by peripheral neuropathy, one with a chronic ataxic peripheral neuropathy and the other with a classical Charcot-Marie-Tooth phenotype. An axonal sensorimotor peripheral neuropathy was described at neurophysiology. A missense heterozygous mutation, c.794A> G (p.Tyr265Cys), in the NEFL gene was found in both patients. This is the first Portuguese family reported with NEFL-related CMT type 2. PMID: 31788662 [PubMed - in process]
Source: Acta Myologica - Category: Neurology Tags: Acta Myol Source Type: research

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Oxaliplatin therapy can be complicated by chemotherapy-induced peripheral neuropathy (CIPN). Other neurotoxic chemotherapies have been linked to single nucleotide variants (SNV) in Charcot-Marie-Tooth disease (CMT) genes. Whether oxaliplatin carries increased risks of CIPN due to SNV in CMT-associated genes is unknown.353 patients receiving oxaliplatin in NCCTG N08CB were serially evaluated for CIPN using a validated patient-reported outcome (PRO) instrument, the CIPN20 questionnaire (sensory scale).
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Source Type: research
Charcot-Marie-Tooth (CMT) is a hereditary condition that affects the myelin sheath of peripheral nerves causing muscle weakness, atrophy, and peripheral neuropathy. This is a firsthand reflection of living with CMT disease from my personal experience and through my family. I hope this provides informative education to practitioners or individuals who may not be familiar with CMT.
Source: Journal of Neuroscience Nursing - Category: Neuroscience Tags: Reflections Source Type: research
In this study, we analyzed a peripheral neuropathy caused by pathogenic variants in the HINT1 gene and evaluated its contribution to the hereditary neuropathy structure. The studied group included 1596 non-related families diagnosed with hereditary motor and sensory neuropathy (HMSN). The results show that HINT1 gene pathogenic variants make a significant contribution to the hereditary neuropathy epidemiology in Russian patients. They account for at least 1.9% of all HMSN cases and 9% of axonopathy cases. The most common HINT1 pathogenic variant in Russian patients is the c.110G>C (p.Arg37Pro) substitution. Its allelic ...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
The X-linked form of Charcot-Marie-Tooth disease type 1 (CMTX1) is an inherited peripheral neuropathy that arises in patients with mutations in the gap-junction beta-1 gene (GJB1).
Source: BMC Neurology - Category: Neurology Authors: Tags: Case report Source Type: research
This article is protected by copyright. All rights reserved. PMID: 31769568 [PubMed - as supplied by publisher]
Source: Cell Biology International - Category: Cytology Authors: Tags: Cell Biol Int Source Type: research
Gene therapy approaches are being deployed to treat recessive genetic disorders by restoring the expression of mutated genes. However, the feasibility of these approaches for dominantly inherited diseases — where treatment may require reduction in the expression of a toxic mutant protein resulting from a gain-of-function allele — is unclear. Here we show the efficacy of allele-specific RNAi as a potential therapy for Charcot-Marie-Tooth disease type 2D (CMT2D), caused by dominant mutations in glycyl-tRNA synthetase (GARS). A de novo mutation in GARS was identified in a patient with a severe peripheral neuropath...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Abstract Length-dependent axonal degeneration is the pathologic hallmark of several neurodegenerative disorders, including inherited peripheral neuropathies (Charcot-Marie-Tooth disease, CMT). CMT is currently an untreatable disorder. This is partially due to lack of translational models suitable for drug discovery. In vitro models of CMT have been hindered by the two-dimensional configuration of neuronal cultures, which limits visualization and orientation of axons. To overcome these limitations, we cultured iPSC-derived spinal motor neurons as three-dimensional spheroids, which grow axons in a centrifugal fashio...
Source: Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Pharmacol Ther Source Type: research
AbstractCharcot-Marie-Tooth disease type-4J (CMT4J), an autosomal recessively inherited peripheral neuropathy characterized by neuronal degeneration, segmental demyelination, and limb muscle weakness, is caused by compound heterozygous mutations in theSAC3/FIG4 gene, resulting in SAC3/FIG4 protein deficiency. SAC3/FIG4 is a phosphatase that not only turns over PtdIns(3,5)P2 to PtdIns3P but also promotes PtdIns(3,5)P2 synthesis by activating the PIKFYVE kinase that also makes PtdIns5P. Whether CMT4J patients have alterations in PtdIns(3,5)P2,  PtdIns5P or in other phosphoinositides (PIs), and if yes, in what direction ...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
Abstract The eye imaginal disc-specific knockdown of dFIG4, a Drosophila homolog of FIG4 that is one of the Charcot-Marie-Tooth disease (CMT)-causing genes, induces an aberrant adult compound eye morphology, the so-called rough eye phenotype. We previously performed modifier screening on the dFIG4 knockdown-induced rough eye phenotype and identified several genes, including CR18854, encoding a long non-coding RNA (lncRNA) as genetic interactants with dFIG4. In the present study, in more extensive genetic screening, we found that the deletion of a gene locus encoding both Odorant rector 46a (Or46a) and lncRNA CR434...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research
Abstract Charcot-Marie-Tooth (CMT) disease is a progressive and heterogeneous inherited peripheral neuropathy. A myriad of genetic factors have been identified that contribute to the degeneration of motor and sensory axons in a length-dependent manner. Emerging biological themes underlying disease include defects in axonal trafficking, dysfunction in RNA metabolism and protein homeostasis, as well deficits in the cellular stress response. Moreover, genetic contributions to CMT can have overlap with other neuropathies, motor neuron diseases (MNDs) and neurodegenerative disorders. Recent progress in understanding th...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research
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