Point mutations in the coding region of the myelin genes, peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) or connexin 32 (Cx32) have been reported in CMT patients, including CMT type 1 (CMT1), CMT type 2 (CMT2) and Déjérine-Sottas neuropathy (DS) patients, and only in the coding region of PMP22 in HNPP families lacking a deletion.
Mutations in 3 distinct myelin genes, PMP22, P0, and connexin 32 cause the 3 major demyelinating subtypes of Charcot-Marie-Tooth (CMT) disease, CMT1A, CMT1B and CMTX, respectively.
In support of this hypothesis, we have identified one recessive and two dominant missense mutations in EGR2 (within regions encoding conserved functional domains) in patients with congenital hypomyelinating neuropathy (CHN) and a family with Charcot-Marie-Tooth type 1 (CMT1).
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).
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.
This "de novo" mutation in a patient presenting with clinical features quite distinct from those of the more frequent Charcot-Marie-Tooth type 1B disease (CMT1B) or Dejerine-Sottas syndrome (DSS) confirms that CH is allelic with other disorders characterized by a less severe phenotype and a different clinical and neuropathological profile.
Charcot-Marie-Tooth type 1 (CMT1) is the most common form and is usually a mild disease with onset in the first or second decade; however there is a interfamilial and intrafamilial clinical variation, ranging from asymptomatic expression to severe muscular weakness and atrophy.
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.
In order to determine the optimal approach for mutation testing in the form of Charcot-Marie-Tooth (CMT) neuropathy, consecutive patients with a CMT phenotype, available family history information on at least first-degree relatives, and median motor conduction velocities of less than 50 m/sec were tested for the CMT1A duplication and for connexin32, peripheral myelin protein 22 (PMP22) and myelin protein zero (P0) point mutations.
Mutations in the peripheral myelin protein zero and connexin32 genes detected by non-isotopic RNase cleavage assay and their phenotypes in Japanese patients with Charcot-Marie-Tooth disease.
The major Charcot- Marie-Tooth Type 1 (CMT1) locus, CMT1A, and Hereditary neuropathy with liability to pressure palsies (HNPP) cosegregate with a 1.5-Mb duplication and a 1.5-Mb deletion, respectively, in band 17p11.2.
Charcot-Marie-Tooth disease (CMT), or hereditary motor and sensory neuropathy (HMSN), includes two main subtypes of CMT1/HMSN I (demyelinating), and CMT2/HMSN II (axonal).
Charcot-Marie-Tooth neuropathy type 1 (CMT1), the most common hereditary neurological disorder in humans, is characterized by clinical and genetic heterogeneity.