Charcot–Marie–Tooth disease: Genetics, epidemiology and complications

Background and aims: Charcot Marie Tooth disease (CMT) is the most prevalent hereditary neuropathy and its frequency is 1 in 2500. CMT is a heterogeneous disease and has different clinical symptoms. The prevalence of CMT and involved genes differ in different countries. CMT patients experience considerable sleep problems and a higher risk of decreased quality of life. In this work it was aimed to provide a review on the genetic and epidemiologic aspects of this disease. Methods: In the current review article, we performed a literature search on the epidemiology of Charcot–Marie–Tooth disease” and provided a brief review on epidemiology, genetic, and complications of CMT. Databases Web of Science and PubMed were searched using the Endnote software for the publications on CMT during 2000 to 2016. Results: Charcot Marie Tooth disease has different prevalence around the world and is the most common neuropathy. Epidemiological studies have estimated the prevalence of CMT in Japan 1/9200, in Iceland 1/8300, in Spain 1/3500 and in Italy 1/5700.The patients have different phenotype and the age of onset. There is a variety of inherited patterns of disease and many genes have been identified responsible whose mutations are main cause of the disease. Conclusion: Due to the impact of this kind of disabilities on the national health, further studies seem to be necessary to gain better knowledge of the disease particularly in the regions with higher prevalence. Moreover molecular biology services offered by genetic laboratories can reduce the incidence of disorder

Investigation on the deletion and duplication of PMP22 gene in patients with Charcot-Marie-Tooth using Real-time PCR in Chaharmahal and Bakhtiari and Isfahan Provinces

Background and aims: Charcot-Marie-Tooth (CMT) is a common sensory-motor polyneuropathy with a prevalence of 1/2500. It is divided into different subgroups and has various hereditary patterns. Among the different subgroups of CMT, type 1A is the most prevalent form of the disease, which is created due to the duplication of the PMP22 gene. In patients has a deletion in the PMP22 gene, the hereditary neuropathic disease is known to be liable to pressure. The aim of this study was to identify the patients affected by the disease with the new, simple, and fast qPCR method and to investigate the appropriateness of this method in evaluating these types of mutations. Methods: In this analytical-descriptive study (code:IR.SKUMS.REC.1394.152), gene duplication and deletion in the patients were studied using the Excel software. The blood samples of 15 families afflicted with CMT and 49 healthy individuals were collected in EDTA anticoagulant tubes and analyzed. DNA extraction and quantitative real-time PCR method were applied for the PMP22 gene as the target gene and the albumin gene as the internal control gene. Results: Two genes were compared in each patient, and it was found that 46% of the subjects had duplication in the PMP22 gene. Conclusion: The qPCR method is an easy and fast way to detect gene duplication and deletion in CMT patients. It does not require any statistical software and can be performed without needing for parental DNA. In addition, the results of this study are consistent with the results of various studies in some countries of the world where the highest levels of deletion and duplication in PMP22 gene are seen. Keywords: CMT1A, PMP22 gene, Quantitative real-time PC

INTRODUCTION Charcot-Marie-Tooth disease: Genetics, epidemiology and complications

ABSTRACT Background and aims: Charcot Marie Tooth disease (CMT) is the most prevalent hereditary neuropathy and its frequency is 1 in 2500. CMT is a heterogeneous disease and has different clinical symptoms. The prevalence of CMT and involved genes differ in different countries. CMT patients experience considerable sleep problems and a higher risk of decreased quality of life. In this work it was aimed to provide a review on the genetic and epidemiologic aspects of this disease. Methods: In the current review article, we performed a literature search on the epidemiology of Charcot-Marie-Tooth disease" and provided a brief review on epidemiology, genetic, and complications of CMT. Databases Web of Science and PubMed were searched using the Endnote software for the publications on CMT during 2000 to 2016. Results: Charcot Marie Tooth disease has different prevalence around the world and is the most common neuropathy. Epidemiological studies have estimated the prevalence of CMT in Japan 1/9200, in Iceland 1/8300, in Spain 1/3500 and in Italy 1/5700.The patients have different phenotype and the age of onset. There is a variety of inherited patterns of disease and many genes have been identified responsible whose mutations are main cause of the disease. Conclusion: Due to the impact of this kind of disabilities on the national health, further studies seem to be necessary to gain better knowledge of the disease particularly in the regions with higher prevalence. Moreover molecular biology services offered by genetic laboratories can reduce the incidence of disorder

In silico and in vitro effects of the I30T mutation on myelin protein zero instability in the cell membrane

Charcot-Marie-Tooth (CMT) diseases are a heterogeneous group of genetic peripheral neuropathies caused by mutations in a variety of genes, which are involved in the development and maintenance of peripheral nerves. Myelin protein zero (MPZ) is expressed by Schwann cells, and MPZ mutations can lead to primarily demyelinating polyneuropathies including CMT type 1B. Different mutations demonstrate various forms of disease pathomechanisms, which may be beneficial in understanding the disease cellular pathology. Our molecular dynamics simulation study on the possible impacts of I30T mutation on the MPZ protein structure suggested a higher hydrophobicity and thus lower stability in the membranous structures. A study was also conducted to predict native/mutant MPZ interactions. To validate the results of the simulation study, the native and mutant forms of the MPZ protein were separately expressed in a cellular model, and the protein trafficking was chased down in a time course pattern. In vitro studies provided more evidence on the instability of the MPZ protein due to the mutation. In this study, qualitative and quantitative approaches were adopted to confirm the instability of mutant MPZ in cellular membranes