Charcot-Marie-Tooth (CMT) is one of the most common hereditary neurological diseases and is divided into different subtypes (CMT1, CMT2, CMT4, CMTX, etc.), each with different modes of inheritance, age of onset of the symptoms and severity as well as variable disease progression.
CMT constitutes a broad group of diseases caused by mutations in several genes that regulate normal functioning of peripheral nerves. A typical feature of the disease is loss of muscle tissue and touch sensation, mainly in the legs but at an advanced stage is also manifested in the upper extremities.
Due to the significant genetic heterogeneity of the disease (>30 genes implicated) but also because of the many clinical sub-types of the disease, which share many common clinical symptoms, genetic testing of patients is often impractical through conventional single-gene testing.
This is particularly true for patients who have tested negative for the relatively frequent types CMT1A and CMTX, where further genetic testing is a diagnostic odyssey. In these patients there are typically no informative criteria to guide towards a specific gene to be tested.
Nevertheless, family planning but also the prognosis often require a specific genetic diagnosis of the disease type and possible treatment options depend on the knowledge of the underlying genetic causes of the CMT patient.
Recognizing these important diagnostic limitations and in an order to contribute positively towards a solution, InterGenetics has developed and offers an NGS panel for the genomic analysis of 42 genes, which we now know to be associated with all known types of Charcot-Marie-Tooth disease and related neuropathies, irrespective of the mode of inheritance.
We perform DNA sequence analysis, via Next Generation Sequencing (NGS) on a Genome Analyzer – Ion Proton platform, of all exons and intron-exon junctions/splice sites of the 42 genes, allowing us to detect >98% of all pathogenic mutations of the genes through the use of specially developed bioinformatics tools.
Where possible and/or necessary, we carry out additional MLPA analysis in order to detect deletions/duplications of the genes (please consult the final test report).
The test is highly sensitive and complex, so it is necessary that the results are assessed by a specialized team of clinical and molecular geneticists, in order to ensure safe and reliable testing.
Proper clinical genetic assessment and genetic counseling, both before and after testing, is essential in order to determine the optimum testing strategy and also to communicate properly the concepts of pathological and normal.