scholarly journals The expanding genetic landscape of hereditary motor neuropathies

Brain ◽  
2020 ◽  
Author(s):  
Danique Beijer ◽  
Jonathan Baets
Keyword(s):  
Motor Neurons ◽  
Underlying Disease ◽  
Dna Integrity ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Causal Genes ◽  
Genetic Landscape ◽  
Inherited Neuropathies ◽  
Underlying Pathophysiology ◽  
Tooth Disease

Abstract Hereditary motor neuropathies are clinically and genetically diverse disorders characterized by length-dependent axonal degeneration of lower motor neurons. Although currently as many as 26 causal genes are known, there is considerable missing heritability compared to other inherited neuropathies such as Charcot-Marie-Tooth disease. Intriguingly, this genetic landscape spans a discrete number of key biological processes within the peripheral nerve. Also, in terms of underlying pathophysiology, hereditary motor neuropathies show striking overlap with several other neuromuscular and neurological disorders. In this review, we provide a current overview of the genetic spectrum of hereditary motor neuropathies highlighting recent reports of novel genes and mutations or recent discoveries in the underlying disease mechanisms. In addition, we link hereditary motor neuropathies with various related disorders by addressing the main affected pathways of disease divided into five major processes: axonal transport, tRNA aminoacylation, RNA metabolism and DNA integrity, ion channels and transporters and endoplasmic reticulum.

scholarly journals PROGRESS IN CLINICAL NEUROSCIENCES: Charcot-Marie-Tooth Disease and Related Inherited Peripheral Neuropathies

2001 ◽  
Vol 28 (3) ◽  
pp. 199-214 ◽  
Author(s):  
Timothy J. Benstead ◽  
Ian A. Grant
Keyword(s):  
Molecular Genetic ◽  
Charcot Marie Tooth ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathy ◽  
Molecular Aspects ◽  
The Many ◽  
Inherited Neuropathies ◽  
Tooth Disease

The classification of Charcot-Marie-Tooth disease and related hereditary motor and sensory neuropathies has evolved to incorporate clinical, electrophysiological and burgeoning molecular genetic information that characterize the many disorders. For several inherited neuropathies, the gene product abnormality is known and for others, candidate genes have been identified. Genetic testing can pinpoint a specific inherited neuropathy for many patients. However, clinical and electrophysiological assessments continue to be essential tools for diagnosis and management of this disease group. This article reviews clinical, electrophysiological, pathological and molecular aspects of hereditary motor and sensory neuropathies.

scholarly journals A murine model of Charcot-Marie-Tooth disease 4F reveals a role for the C-terminus of periaxin in the formation and stabilization of Cajal bands

2018 ◽  
Vol 3 ◽  
pp. 20 ◽  
Author(s):  
Diane L. Sherman ◽  
Peter J. Brophy
Keyword(s):  
Plasma Membrane ◽  
Schwann Cell ◽  
Laminin Receptor ◽  
Cell Plasma Membrane ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
C Terminus ◽  
Cell Plasma ◽  
Inherited Neuropathies ◽  
Tooth Disease

Charcot-Marie-Tooth (CMT) disease comprises up to 80 monogenic inherited neuropathies of the peripheral nervous system (PNS) that collectively result in demyelination and axon degeneration. The majority of CMT disease is primarily either dysmyelinating or demyelinating in which mutations affect the ability of Schwann cells to either assemble or stabilize peripheral nerve myelin. CMT4F is a recessive demyelinating form of the disease caused by mutations in the Periaxin (PRX) gene. Periaxin (Prx) interacts with Dystrophin Related Protein 2 (Drp2) in an adhesion complex with the laminin receptor Dystroglycan (Dag). In mice the Prx/Drp2/Dag complex assembles adhesive domains at the interface between the abaxonal surface of the myelin sheath and the cytoplasmic surface of the Schwann cell plasma membrane. Assembly of these appositions causes the formation of cytoplasmic channels called Cajal bands beneath the surface of the Schwann cell plasma membrane. Loss of either Periaxin or Drp2 disrupts the appositions and causes CMT in both mouse and man. In a mouse model of CMT4F, complete loss of Periaxin first prevents normal Schwann cell elongation resulting in abnormally short internodal distances which can reduce nerve conduction velocity, and subsequently precipitates demyelination. Distinct functional domains responsible for Periaxin homodimerization and interaction with Drp2 to form the Prx/Drp2/Dag complex have been identified at the N-terminus of Periaxin. However, CMT4F can also be caused by a mutation that results in the truncation of Periaxin at the extreme C-terminus with the loss of 391 amino acids. By modelling this in mice, we show that loss of the C-terminus of Periaxin results in a surprising reduction in Drp2. This would be predicted to cause the observed instability of both appositions and myelin, and contribute significantly to the clinical phenotype in CMT4F.

Diaphragmatic Dysfunction in Siblings with Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)

CHEST Journal ◽  
1987 ◽  
Vol 91 (4) ◽  
pp. 567-570 ◽  
Author(s):  
Charles K. Chan ◽  
Vahid Mohsenin ◽  
Jacob Loke ◽  
Jim Virgulto ◽  
M. Leonide Sipski ◽  
...  
Keyword(s):  
Sensory Neuropathy ◽  
Diaphragmatic Dysfunction ◽  
Charcot Marie Tooth ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease ◽  
Motor And Sensory Neuropathy

Allelic heterogeneity in hereditary motor and sensory neuropathy type la (Charcot-Marie-Tooth disease type 1a)

Neurology ◽  
1993 ◽  
Vol 43 (5) ◽  
pp. 1010-1010 ◽  
Author(s):  
J. E. Hoogendijk ◽  
E.A.M. Janssen ◽  
A. A.W.M. Gabreels-Festen ◽  
G. W. Hensels ◽  
E. M.G. Joosten ◽  
...  
Keyword(s):  
Sensory Neuropathy ◽  
Disease Type ◽  
Allelic Heterogeneity ◽  
Charcot Marie Tooth ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease ◽  
Motor And Sensory Neuropathy

Cochlear implantation in a patient with deafness induced by Charcot–Marie–Tooth disease (hereditary motor and sensory neuropathies)

2006 ◽  
Vol 120 (6) ◽  
pp. 508-510 ◽  
Author(s):  
J T F Postelmans ◽  
R J Stokroos
Keyword(s):  
Cochlear Implantation ◽  
Transmembrane Domain ◽  
Point Mutations ◽  
Auditory Neuropathy ◽  
Heterogeneous Group ◽  
Charcot Marie Tooth ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Close Proximity ◽  
Tooth Disease

Charcot–Marie–Tooth disease (CMT), also named hereditary motor and sensory neuropathies (HMSN), comprises a clinically and genetically heterogeneous group of disorders affecting the peripheral nervous system. Deafness induced by CMT is clinically distinct among the genetically heterogeneous group of CMT disorders. Deafness in CMT patients is associated with point mutations or deletions in the transmembrane domain in the peripheral myelin gene (PMP) 22, which are in close proximity to the extracellular component of this gene. We present a patient with deafness induced by CMT type 1A, undergoing cochlear implantation. Prior investigations showed good results due to replacing a synchronous impulse by means of cochlear implantation in patients with auditory neuropathy.

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