Nemaline Myopathy Panel (7 Genes) Test Details
Nemaline myopathy is a genetically heterogeneous type of congenital myopathy that is defined based on the presence of nemaline rods in muscle biopsies. Individuals with nemaline myopathy typically present at birth or in childhood with hypotonia, muscle weakness, and depressed or absent deep tendon reflexes. The disease can be inherited in autosomal dominant or autosomal recessive manner. For more information about nemaline myopathy, please visit: http://www.ncbi.nlm.nih.gov/books/NBK1288/
Current tests for Nemaline Myopathy
Nemaline Myopathy Panel - 7 genes
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|ACTA1||Actin, Alpha, Skeletal Muscule 1||102610||1q42.13|
|TNNT1||Troponin T1, Skeletal, Slow||191041||19q13.42|
The Nemaline Myopathy Panel should be ordered for individuals with a clear diagnosis of nemaline 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 Nemaline Myopathy Panel is approximately 75% for patients diagnosed with nemaline myopathy (GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1288/; Malfatti 2014: PubMed ID 24725366).