A nonsense mutation in myelin protein zero causes congenital hypomyelination neuropathy through altered P0 membrane targeting and gain of abnormal function.
Charcot-Marie-Tooth disease (CMT) type 1A is the most common form of CMT 1 and one of the autosomal dominant demyelinating hereditary motor and sensory neuropathies (HMSN).
This study broadens the clinical phenotype of hereditary motor and sensory neuropathy due to MPZ mutation and emphasises the difficulty of achieving an accurate genetic diagnosis in a sporadic patient to provide an appropriate pharmacologic treatment.
Patient's family history suggested an autosomal dominant inheritance.Molecular testing revealed both, a hereditary motor and sensory neuropathy type 1A (HMSN1A, also called Charcot-Marie-Tooth neuropathy 1A, CMT1A) due to a PMP22 gene duplication and facioscapulohumeral muscular dystrophy (FSHD) due to a partial deletion of the D4Z4 locus (19 kb).
19 adults with known mitochondrial mutation (MT) have been assessed with the Stanford Health Assessment Questionnaire 20-item Disability Index (HAQ-DI), the Symptom Check List-90-Revised (SCL-90-R), the Beck Depression Inventory-Short Form (BDI-SF), the Hamilton Depression Rating Scale (HDRS) and the clinical version of the Structured Clinical Interview for the the DSM-IV (SCID-I and SCID-II) As control, 10 patients with hereditary sensorimotor neuropathy (HN), harboring the peripheral myelin protein-22 (PMP22) mutation were examined with the same tools.
Mutations in the myelin protein zero (MPZ) gene are the third most frequent cause of hereditary motor and sensory neuropathies (HMSN), also called Charcot-Marie-Tooth disorders (CMT).
Hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous neuropathies classically divided into demyelinating (CMT1) and axonal forms (CMT2).
One hundred fifty index patients with HMSN and a median motor nerve conduction velocity of 25 m/s or greater and without mutations in the genes encoding connexin 32 and myelin protein zero.
Myelin protein zero mutation His39Pro: hereditary motor and sensory neuropathy with variable onset, hearing loss, restless legs and multiple sclerosis.
We present detailed assessments of patients with CMT1A and CMTX, including nerve biopsy, and conclude that coexistent inflammatory neuropathy is not genotype-specific in hereditary motor and sensory neuropathy.
The prevalence of the Hereditary Motor and Sensory Neuropathy Type 1A (HMSN 1A or Charcot-Marie-Tooth Neuropathy 1A, CMT1A) alone is estimated to be as high as 1/5000.
The recognized CMT2 genotypes include: CMT2A (mapped to chromosome 1p35-36); CMT2B (3q13-22); CMT2C (with vocal cord paresis); CMT2D (7p14); CMT2E, related to a mutation in the NF-L gene on chromosome 8p21; proximal CMT2, or HMSN P (3q13.1); CMT2 with MPZ mutations; autosomal recessive CMT2 (1q21.2-q21.3); agenesis of the corpus callosum with sensorimotor neuronopathy (15q13-q15); CMT2 X-linked with deafness and mental retardation (Xq24-q26).
To report a novel hereditary motor and sensory neuropathy (HMSN) phenotype, with partial steroid responsiveness, caused by a novel dominant mutation in the myelin protein zero (MPZ) gene.
A moderate increase in the number of PMP22 genes led to hypomyelination comparable to CMT1A, whereas high copy numbers of transgenic PMP22 resulted in phenotypes resembling more severe forms of hereditary motor and sensory neuropathies.
The present findings further extend the range of phenotypes associated with PMP0 mutations and indicate that families with "intermediate" HMSN need not necessarily be X-linked as previously suggested.