Mutations in three genes coding for the myelin proteins peripheral myelin protein 22, myelin protein zero and connexin 32 and in one gene coding for the transcription factor early growth response 2 element are associated with Charcot-Marie-Tooth type 1 and 2, hereditary neuropathy with liability to pressure palsies, Dejerine-Sottas syndrome and congenital hypomyelination.
Duplication within the chromosome 17p11.2 (CMT1Adup), peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and gap junction beta1-protein (GJB1) gene mutations are frequent causes of the Charcot-Marie-Tooth disease (CMT).
We investigated the presence of duplication in chromosome 17p11.2 in 4 individuals with sporadic Charcot-Marie-Tooth disease (CMT 1) and 1 isolated case where a definite differential diagnosis between CMT 1 and Déjérine-Sottas disease was not achieved.
We performed a mutational analysis of NEFL in a series of 177 index cases with CMT and without mutations in the genes for peripheral myelin protein zero (MPZ), peripheral myelin protein 22 (PMP22) and connexin 32 (GJB1); the motor nerve conduction velocity (MNCV) at the median nerve was below 38 m/s in 76 cases and above 38 m/s in 101.
We analysed the nerve specific promoter of the peripheral myelin protein 22 gene (PMP22) in a set of 15 unrelated patients with Charcot-Marie-Tooth type 1 disease (CMT1) and 16 unrelated patients with hereditary neuropathy with liability to pressure palsies (HNPP).
A nonsense mutation in myelin protein zero causes congenital hypomyelination neuropathy through altered P0 membrane targeting and gain of abnormal function.
We found in the present study that LMW slow TnT was significantly upregulated in demyelination form type 1 CMT (CMT1) but not axonal form type 2 CMT (CMT2) muscles.
Two major types can be distinguished based on electrophysiologic phenotypes: CMT type 1 (CMT1) displays uniformly decreased nerve conduction velocity associated with a demyelinating hypertrophic neuropathy, and CMT type 2 (CMT2) displays normal or near-normal nerve conduction velocity associated with a neuronal defect.
To evaluate, by skin biopsy, dermal nerve fibers in 31 patients with 3 common Charcot-Marie-Tooth (CMT) genotypes (CMT1A, late-onset CMT1B, and CMTX1), and rarer forms of CMT caused by mutations in RAB7 (CMT2B), TRPV4 (CMT2C), and GDAP1 (AR-CMT2K) genes.
We observed a missense mutation in the peripheral myelin protein zero gene (MPZ, Thr124Met) in seven Charcot-Marie-Tooth (CMT) families and in two isolated CMT patients of Belgian ancestry.
CMT1 (motor conduction velocity (MCV) <38 m/s), CMT2 (MCV >38 m/s) and CMT intermediate (MCV 25-45 m/s) were found in 48.2%, 49.4% and 2.4% of the families.
A European collaboration on Charcot-Marie-Tooth type 1 (CMT1) disease and hereditary neuropathy with liability to pressure palsies (HNPP) was established to estimate the duplication and deletion frequency, respectively, on chromosome 17p11.2 and to make an inventory of mutations in the myelin genes, peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32) located on chromosomes 17p11.2, 1q21-q23 and Xq13.1, respectively.
Pathomechanistic and therapeutic target advances in CMT include the identification of the ErbB receptor signalling pathway as a therapeutic target in CMT1A and pharmacological modification of the unfolded protein response in CMT1B.
Charcot-Marie-Tooth neuropathy (CMT) type 1 is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), the X chromosome (CMTX), and to another unknown autosome (CMT1C).