Identifying molecular pathways involved in early and late onset CMT1B will be crucial to understand how MPZ mutations cause CMT1B so that rational therapies for both early and late onset neuropathies can be developed.
Some mutations of MPZ cause severe early-onset neuropathies such as Dejerine-Sottas disease, while others cause the classical CMT phenotype with normal early milestones but development of disability during the first two decades of life.
However, involvement of the autonomic nervous system in this type of neuropathy is unclear and further studies are required to elucidate the role of the MPZ gene in the autonomic nervous system.
Daily administration of progesterone elevated the steady-state levels of Pmp22 and Mpz mRNA in the sciatic nerve, resulting in enhanced Schwann cell pathology and a more progressive clinical neuropathy.
Molecular genetic testing and particularly screening for MPZ mutations in late onset neuropathies are important to differentiate acquired and inherited neuropathies.
We conclude that DSS, although in general denoting a more serious neuropathy than CMT1, does not imply a severe disability or wheelchair dependency in adult life.
This broadens the range of familial neuropathy associated with MPZ mutations to include steroid responsive neuropathy, initially diagnosed as chronic inflammatory demyelinating polyneuropathy.
Family study revealed that de novo Ile62Phe mutation on the MPZ gene occurred in the proband and was inherited by her children with early onset slowly progressive neuropathy.
Motor and sensory neuropathies with the clinical features of HMSN III (Dejerine-Sottas syndrome, DSS) are etiologically related to heterozygous mutations in either peripheral myelin protein-22 (PMP22) or myelin protein zero (MPZ).
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.
Genetic heterogeneity within the most common genetic neuropathy, Charcot-Marie-Tooth disease (CMT) results in about 70% slow nerve conduction CMT1 and 30% normal nerve conduction CMT2.
In this study we excluded all four regions for the presence of distal HMN II, indicating that this neuropathy is genetically different from CMT 1 and recessive SMA.
Exenatide-induced phosphorylation of p38 and CREB was also totally blocked by the PKA inhibitor and siRNA/p38<i>β</i>, but not by siRNA/p38<i>α</i> Seven-day intrathecal injections of siRNA/p38<i>β</i> (but not siRNA/p38<i>α</i>) completely blocked exenatide-induced spinal p38 activation, <i>β</i>-endorphin expression, and mechanical antiallodynia in rats with established neuropathy, although siRNA/p38<i>β</i> and siRNA/p38<i>α</i> were not antiallodynic.
VAC14 should be prioritized for further validation of its potential role as a predictor of docetaxel-induced neuropathy and biomarker for treatment individualization.