diagnostic laboratory challenges about charcot-marie-tooth disease

charcot-marie-tooth disease (cmt) is the most common inherited neurological disorder, affecting both motor and sensory peripheral nerves. neurophysiological patterns divide cmt into three main groups: demyelinating cmt1 (upper limb motor nerve conduction velocity (mncv) <38 m/s), axonal cmt2 (mncv >38 m/s) and intermediate cmt (mncv 25-45 m/s). cmt has been also categorized based on the mode of inheritance and subtypes are defined according to the mutant genes. duplication of 1.5 mb of chromosome 17, encompassing pmp22 gene, accounts for up to 80% of cases with demyelinating neuropathies in its most prevalent type, cmt1a. deletion of the same region is responsible for hereditary neuropathy with liability to pressure palsies (hnpp). the clinical and genetic heterogeneity of cmt disease has been always considered as one of the major challenges in diagnostic procedure. although, most current genetic testing strategies for cmt are mainly based on the family history and data on clinical and neurophysiological assessments, variable degree of phenotypic expression and large number of genes involved in cmt bring challenges to the diagnosis. hence, in everyday practice in genetic laboratories, the detection rate for this group of patients may significantly influenced by this genetic and clinical heterogeneity. our aim was to present our experience on the applicability of the recommended strategies for cmt diagnosis.  dosage analysis using multiplex ligation probe amplification (mlpa), a specific and sensitive quantitative method, is considered as the first step in the detection of demyelinating cmt. mlpa analysis of 30 unrelated individuals who were referred to kariminejad-najmabadi pathology and genetics center  with general diagnosis of polyneuropathy, revealed 7 cases of cmt1a (due to 1.5 mb duplication) and a case with hnpp (1.5 mb deletion).  this detection rate of about 25% for mlpa testing elucidates the need for a better understanding of the circumstances under which the genetic test is requested. considering the clinical data, when mlpa fails to detect the causative gene, patients are supposed to be subjected to extended analysis. implementation of ngs in diagnosis of cmt has made a powerful platform to detect the full spectrum of cmt mutations, which provides an efficient and cost effective genetic testing and therefore an increased detection rate.