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The complex genetic background of inherited peripheral neuropathy or Charcot-Marie-Tooth disease (CMT) is incompletely understood. Variants in ITPR3, encoding inositol 1,4,5-trisphosphate receptor type 3, have previously been proposed as candidate causes of CMT but the association has not been confirmed as no further patients have been found and no functional studies performed on the mutations until now. The inositol 1,4,5-trisphosphate receptors regulate multiple cellular processes by releasing Ca2+ from the ER.
Conclusions. The nerve roots of CIDP, Charcot-Marie-Tooth disease type-1, and polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes syndrome were difficult to distinguish by MRN. Atypical CIDP patients had less nerve root injury compared with typical CIDP patients. MRN of either the brachial plexus or the lumbosacral plexus had a high diagnostic accuracy for CIDP, and it is not necessary to perform both parts of the examination. Level of Evidence: 2
Charcot Marie Tooth (CMT) is an inherited progressive peripheral neuropathy characterized by prominent muscle weakness and sensory loss. Typical presentation includes high medial arches and tibialis anterior muscle weakness, which results in foot drop and leads to an increased frequency of falls. For this reason, foot drop is frequently the target of intervention. Reliably quantifying severity of foot drop and tibialis anterior muscle weakness is difficult through observational gait analysis and strength testing.
ConclusionThe finding of aHADHA mutation as a cause of CMT is of interest because its encoded protein is a subunit of the mitochondrial trifunctional protein (MTP) complex, a mitochondrial enzyme involved in long chain fatty acid oxidation. Long chain fatty acid oxidation is an important source of energy for skeletal muscles. The mutation found in CMT2-102 is only the second intronic mutation reported inGDAP1. The mutation in the CMT2-102 pedigree was outside the canonical splice site sequences, emphasizing the importance of careful examination of available intronic sequences in exome sequence data.
Central nervous system involvement has been described in peripheral neuropathies, including different forms of Charcot-Marie-Tooth (CMT) disease. The aim of our study was to systematically investigate possible brain structural modifications in CMT1A patients, using volumetric MRI, and diffusion tensor imaging (DTI). In this prospective cross-sectional study, from May 2017 to May 2019, we acquired 3T MRI brain scans of genetically confirmed CMT1A patients and age- and sex-comparable healthy controls. Patients also underwent clinical and electrophysiological examinations assessing motor and sensory domains. Voxel-based morph...
Publication date: Available online 21 August 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): Anna Maria Giudetti, Flora Guerra, Serena Longo, Raffaella Beli, Roberta Romano, Fiore Manganelli, Maria Nolano, Vincenzo Mangini, Lucio Santoro, Cecilia Bucci
Charcot-Marie-Tooth disease (CMT) is a common inherited peripheral neuropathy that affects one in 2500 people . Charcot-Marie-Tooth type 1 (CMT1), the most prevalent subtype, includes patients with dominantly inherited demyelinating neuropathies and CMT type 2 (CMT2) includes patients with dominantly inherited axonal neuropathies. CMT causes functional impairments at the joint level such as distal limb muscle weakness and sensory loss , with a typical childhood onset and variable rate of disease progression [3, 4].
CONCLUSION: Our results highlight the advantage of using WES for genetic diagnosis in highly heterogeneous diseases such as IPNs. Moreover, functional analysis is required for novel and uncertain variants. PMID: 32657593 [PubMed - in process]
This article is protected by copyright. All rights reserved. PMID: 32385905 [PubMed - as supplied by publisher]
Abstract Small heat shock proteins are ubiquitously expressed chaperones, yet mutations in some of them cause tissue-specific diseases. Here, we will discuss how small heat shock proteins give rise to neurodegenerative disorders themselves while we will also highlight how these proteins can fulfil protective functions in neurodegenerative disorders caused by protein aggregation. The first half of this paper will be focused on how mutations in HSPB1, HSPB3, and HSPB8 are linked to inherited peripheral neuropathies like Charcot-Marie-Tooth (CMT) disease and distal hereditary motor neuropathy (dHMN). The second part ...
Abstract The small GTPase RAB7A regulates late stages of the endocytic pathway and plays specific roles in neurons, controlling neurotrophins trafficking and signaling, neurite outgrowth and neuronal migration. Mutations in the RAB7A gene cause the autosomal dominant Charcot-Marie-Tooth type 2B (CMT2B) disease, an axonal peripheral neuropathy. As several neurodegenerative diseases are caused by alterations of endocytosis, we investigated whether CMT2B-causing mutations correlate with changes in this process. To this purpose, we studied the endocytic pathway in skin fibroblasts from healthy and CMT2B individuals. W...