Genetic approaches and pathogenic pathways in the clinical management of Charcot-Marie-Tooth disease

Abstract

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting at least 1 in 2500 individuals. CMT refers to a heterogeneous group of inherited neuropathies from both phenotypic and genetic points of view. Over the last decades, there have been important advances not only in the identification of causative genes but also in understanding the molecular basis for many forms of CMT. In fact, to date, around 100 genes have been related to CMT disease, thanks to next generation sequencing techniques, and they have been proven to affect either the myelin or axon of peripheral nerves. Moreover, its genetic diagnosis has remarkedly improved, although there are still difficulties when it comes to treatment. In this review, we explore in depth the eight most prevalent genes associated with CMT: GDAP1, GJB1, HINT1, MFN2, MPZ, PMP22, SH3TC2, and SORD. We also address the disrupted cellular processes and pathophysiological mechanisms involved in the disease. A better understanding of the pathogenic mechanisms responsible for each type of CMT would be essential to identifying molecular targets and therapeutic strategies.

Comparative RNAseq analysis for the study of motoneuron diseases in multi-omics approaches

“…To date, researchers have identi ed approximately 100, 380 and 120 genes related to CMT, ataxia and HSP, respectively. 6,7,8 . The cerebellum and corticospinal motoneurons are the primarily affected regions in ataxia and HSP, respectively, while CMT may affect alpha motor neurons or Schwann cells, depending on the subtype.…”

Importance of Electrodiagnostic Testing Prior to a Tethered Cord Release in a Patient with Overlapping Symptoms of Charcot-Marie-Tooth Disease

“…Charcot-Marie-Tooth (CMT) disease, the most frequent hereditary neuromuscular disorder affecting one in 2500 individuals, is a heterogeneous group of motor-sensory length-dependent neuropathies affecting either the myelin and/or axons of peripheral nerves [1,2]. Inherited in an autosomal dominant manner, CMT type 1A (CMT1A) disease is the most common form of CMT disease and is caused by a 1.5 Mb duplication on chromosome 17p11.2 encompassing the gene coding for peripheral myelin protein-22 (PMP22 gene) [1][2][3][4]. This condition is characterized by distal muscle weakness, sensory loss, decreased deep tendon reflexes (DTRs), and skeletal deformities such as pes cavus [1,3,5].…”

“…Inherited in an autosomal dominant manner, CMT type 1A (CMT1A) disease is the most common form of CMT disease and is caused by a 1.5 Mb duplication on chromosome 17p11.2 encompassing the gene coding for peripheral myelin protein-22 (PMP22 gene) [1][2][3][4]. This condition is characterized by distal muscle weakness, sensory loss, decreased deep tendon reflexes (DTRs), and skeletal deformities such as pes cavus [1,3,5]. Common electrodiagnostic (EDX) findings in demyelinating CMT1A disease include diffuse and homogeneous slowing of nerve conduction velocities (NCVs) (ulnar and median motor NCV ≤ 38 m/s) without a conduction block [2][3][4].…”

Aberrant stress granule network is involved in CMT2 neuropathies

“…Charcot-Marie-Tooth (CMT) diseases are the most common inherited peripheral neuropathies with a population prevalence of about 1:2500. 1 CMT diseases are usually characterized with distal weakness, sensory loss and foot deformity, and the symptoms progress slowly, which bring the patients lots of sufferings. CMT patients are classified into different groups, including CMT type 1 (CMT1; demyelinating form), CMT type 2 (CMT2; axonal form) and intermediate CMT form.…”