Charcot-Marie-Tooth disease and related genetic neuropathies.
ABSTRACT The inherited peripheral neuropathies are a complex group of disorders caused by mutations in more than 50 genes. Scientifically, these disorders provide extensive information on molecular pathways that cause demyelination, axonal loss, and abnormal interactions between Schwann cells and the axons they ensheathe. Clinically, however, these neuropathies are confusing because it is difficult to determine what gene to test for in a given patient, inheritance patterns may differ among patients, and genetic testing is expensive. This review provides a biological context and guidelines to help neurologists better understand the basis and focus of genetic testing for these disorders.
In the past 5 years, many of the genetic causes of inherited neuropathies have been discovered and the phenotypes of inherited neuropathies have been characterized. Clinical trials of genetic neuropathies are now underway.
It is hoped that this review will lead to a better understanding of these fascinating neuropathies for health care professionals and that this improved understanding will facilitate treatment advances for these presently untreatable diseases.
SourceAvailable from: Young Bin Hong[Show abstract] [Hide abstract]
ABSTRACT: Mutations in the gene encoding periaxin (PRX) are known to cause autosomal recessive Dejerine-Sottas neuropathy (DSN) or Charcot-Marie-Tooth disease type 4F. However, there have been no reports describing Korean patients with these mutations. We examined a Korean DSN patient with an early-onset, slowly progressive, demyelinating neuropathy with prominent sensory involvement. Whole-exome sequencing and subsequent capillary sequencing revealed novel compound heterozygous nonsense mutations (p.R392X and p.R679X) in PRX. One mutation was transmitted from each of the patient's parents. No unaffected family member had both mutations, and the mutations were not found in healthy controls. We believe that these novel compound heterozygous nonsense mutations are the underlying cause of DSN. The clinical, electrophysiologic, and pathologic phenotypes in this family were similar to those described previously for patients with PRX mutations. We have identified the first PRX mutation in a Korean patient with DSN.Journal of Clinical Neurology 01/2015; 11(1):92-6. DOI:10.3988/jcn.2015.11.1.92 · 1.81 Impact Factor
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ABSTRACT: Introduction: We have identified a large consanguineous Lebanese family with 5 individuals with severe childhood-onset recessive sensory loss associated with deafness and variable optic atrophy. Methods: Autozygosity mapping was performed in all affected individuals, followed by whole-exome sequencing (WES) in 2 individuals. Results: WES identified a homozygous missense mutation (c.916G>A, p.G306R) in the cerebral riboflavin transporter SLC52A2, recently shown to cause Brown-Vialetto-Van-Laere syndrome (BVVLS), which is considered primarily a motor neuronopathy. Our patients have a phenotype distinct from BVVLS, characterized by severe progressive sensory loss mainly affecting vibration and proprioception that evolves to include sensorineural hearing loss in childhood, variable degrees of optic atrophy, and marked upper extremity weakness and atrophy. Treatment of 3 patients with 400 mg/day riboflavin over 3 months produced definite clinical improvement. Discussion: Mutations in SLC52A2 result in a recognizable phenotype distinct from BVVLS. Early recognition of this disorder is critical, given its potential treatability. © 2014 Wiley Periodicals, Inc.Muscle & Nerve 11/2014; 50(5). DOI:10.1002/mus.24224 · 2.31 Impact Factor
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ABSTRACT: This study aimed to conduct a systematic literature review regarding the associations between psychiatric symptoms, functional impairments, and quality of life in patients with CMT. The PUBMED, PsycInfo, SCIELO, and LILACS electronic databases were used, and the following search terms were employed: Charcot-Marie-Tooth, hereditary motor and sensory neuropathy (HMSN), mental disorder, quality of life, psychiatry, psychiatric, and psychological without the use of time-limit filters. According to the adopted inclusion criteria, 20 studies were included and appraised. These studies indicated that patients with CMT exhibited an increased trend toward depressive symptoms compared with the general population. In addition, CMT patients were exposed to a higher risk of reduced quality of life and significant sleep impairment. Considering the comorbidity of CMT with other psychiatric disorders, the heterogeneity of the instruments used to evaluate the psychiatric symptoms compromised the ability to compare the studies examined. Our results indicate a need for a systematic evaluation of these conditions to minimise the impairments and decreased quality of life caused by CMT.ASN Neuro 03/2014; 6(3). DOI:10.1042/AN20130048 · 4.44 Impact Factor