Genomic testing for muscular dystrophies and neuromuscular diseases – 376 genes NGS panel

Collectively, neuromuscular disorders refer to numerous disorders that affect the peripheral nervous system, either by impairing the development and function of the muscles or by disturbing the associated nerves or neuromuscular synapses. This broad category includes more than 400 hereditary diseases, all of which are individually rare, but together have an incidence greater than 1 in 3,000.

Muscular dystrophies comprise the most common but also heterogeneous subgroup with many common clinical symptoms, which include muscle degeneration, loss of muscle mass, progressive muscular weakness, hypotonia and elevated serum levels of the enzyme CPK.

Recently, a large number of genes have been associated with neuromuscular disorders and we have thus expanded our understanding of the molecular basis of these diseases. However, the cause(s) is unknown in the majority of patients, despite clinical and histological evidence. The significant genetic and phenotypic heterogeneity, our inability to correctly identify sporadic and non-sporadic cases and the often overlapping clinical features are great challenges in detecting the underlying genetic causes. Furthermore, neuromuscular disorders in their entirety are manifested in all possible types of inheritance, i.e. as autosomal recessive, autosomal dominant or X-linked.

Furthermore, a number of genes involved in these diseases are large in size (such as TTN, NEB, RYR, DMD, etc.) and the different types of mutations (including deletions/duplications) require a combination of molecular genetics techniques for their detection, which may not be possible in every diagnostic laboratory.

For several years, the traditional method for the genetic diagnosis of these disorders was based on an approach which analyzed one gene at a time through conventional DNA Sanger sequencing, starting from the gene estimated as the most likely to be implicated, based on the clinical symptoms and family history. However, these techniques generally have a low diagnostic yield in the majority of cases and were largely ineffective in providing a successful molecular investigation.

The recent introduction of Next Generation Sequencing (NGS) has now become a highly effective diagnostic strategy, through the parallel analysis of a large number of genes involved in neuromuscular diseases.

InterGenetics has developed and offers an NGS panel for the genomic analysis of 376 genes (see gene list), associated with a wide spectrum of clinical symptoms which include muscular dystrophies, myopathies, congenital myasthenic syndromes, etc., regardless 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 376 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.

The test is executed in 3-4 weeks