Myotubular/Centronuclear Myopathy Panel (5 Genes) Test Details
Myotubular/centronuclear myopathy (CNM) is a group of myopathies defined by the presence of one or more internalized nuclei in affected myofibers without excessive regeneration or additional structural abnormalities. The clinical presentation ranges from severe hypotonia with respiratory insufficiency at birth to late-onset mild muscle weakness. Variants in 5 genes have been identified in patients with CNM up to date: MTM1 in X-linked severe (myotubular) disease, DNM2 in autosomal dominant and sporadic cases, BIN1 and TTN in autosomal recessive CNM, and RYR1 in autosomal recessive and sporadic presentations. Please visit GeneReviews for more information about myotubular/centronuclear myopathy.
Current tests for Myotubular/Centronuclear Myopathy
Myotubular/Centronuclear Myopathy Panel - 5 genes
|BIN1||Briding Integrator 1||601248||2q14.3|
|RYR1||Ryanodine Receptor 1||180901||19q13.2|
The Myotubular/Centronuclear Myopathy Panel should be ordered for individuals with a clear diagnosis of myotubular or centronuclear myopathy based on muscle biopsy. This panel will provide comprehensive coverage of the implicated genes and minimize the incidence of variants of unknown significance compared with the MyoGene panel.
The MyoGene Panel is best suited for individuals who already have exhausted current testing options or those whose clinical diagnosis is not yet clear and may help shorten the “diagnostic odyssey.” While the MyoGene Panel offers comprehensive testing for multiple forms of myopathy, there is a higher likelihood of finding novel variants, which may be more difficult to interpret if it is found in a gene that is not (yet) known to cause the individual’s disease.
This test is performed by next generation sequencing using Agilent SureSelect capture followed by sequencing of the coding regions and splice sites using Illumina sequencing technologies. Variant calls are generated using the Burrows-Wheeler Aligner followed by Genomic Analysis Tool Kit (GATK) analysis. Detection of copy number variants (CNVs) encompassing 1 or more exons is performed using VisCap™ analysis. Sanger sequencing is used to fill in regions with insufficient coverage. All clinically significant variants are confirmed by Sanger sequencing or an alternate assay. Variants classified as likely benign or benign are not confirmed. This test does not detect variants in non-coding regions that could affect gene expression, aside from the splice junctions, and a few exons have been excluded due to technical difficulties. CNV analysis is only performed when data meets necessary quality standards and may not be available for all cases.
Analytical and Clinical Sensitivity
This test is 100.00% sensitive (525/525 variants tested; 95% CI = 99.27-100.00% ) to detect variants changing a single base and 100.00% sensitive to detect insertion/deletions 1-21 bp in size (17/17 variants tested; 95% CI = 81.57-100.00%). Regions with high sequence homology are included in this test if a unique Sanger sequencing assay can be designed to rule out false positive calls. Analytical sensitivity in these regions may be reduced.
The detection rate of the Myotubular/Centronuclear Myopathy Panel is approximately 80% for patients diagnosed with myotubular or centronuclear myopathy (Biancalana 2012: PubMed ID 22617344).