Muscular Dystrophy (LGMD/EDMD) Panel (25 Genes) Test Details
Muscular dystrophies (MD) are a clinically and genetically heterogeneous group of muscle diseases characterized by muscle weakness and wasting that tend to be progressive, with continuous degeneration/regeneration of muscle fibers. Serum creatine kinase (CK) is usually elevated. Muscular dystrophies can be grouped as Duchenne MD, Emery-Dreifuss MD, limb-girdle MD, congenital MD, fascioscapulohumeral MD, etc. depending on the age of onset, distribution of muscle weakness, and underlying genetic cause. Our Muscular Dystrophy panel includes 25 genes associated with Limb-girdle muscular dystrophy (LGMD) and Emery-Dreifuss muscular dystrophy (EDMD). LGMD typically involves weakness and wasting of proximal greater than distal muscles, and can be inherited either in autosomal recessive or autosomal dominant manner. EDMD is characterized by slowly progressive muscle weakness that tends to begin in early childhood with or without joint contractures and/or cardiac involvement. EDMD may be inherited in an X-linked manner due to variants in EMD or FHL1 genes, and in an autosomal dominant or recessive manner due to mutations in LMNA gene. For more information about LGMD and EDMD, please visit: http://www.ncbi.nlm.nih.gov/books/NBK1408/; http://www.ncbi.nlm.nih.gov/books/NBK1436/
Current tests for Muscular Dystrophy
Muscular Dystrophy (LGMD/EDMD) Panel - 25 genes
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|DAG1||Dystrophin-Associated Glycoprotein 1||128239||3p21.31|
|DNAJB6||DNAJ/HSP40 Homolog, Subfamily B, Member 6||611332||7q36.3|
|FHL1||Four-and-a-half Lim Domains 1||300163||Xq26.3|
|ISPD||Isoprenoid Synthase Domain-Containing Protein||614631||7p21.2|
|POMGNT1||Protein O-Mannose Beta-1,2-N-Acetylglucosaminyltransferase||606822||1p34.1|
|POMT1||Protein O-Mannosyltransferase 1||607423||9q34.13|
|POMT2||Protein O0Mannosyltransferase 2||607439||14q24.3|
|TRIM32||Tripartite Motif-Containing Protein 32||602290||9q33.1|
The Muscular Dystrophy (LGMD/EDMD) panel should be ordered for individuals with a clear diagnosis of LGMD or EDMD. 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 Muscular Dystrophy (LGMD/EDMD) Panel is approximately 90% for childhood-onset and 35% for adult-onset LGMD, and 35% for EDMD (GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1408/; http://www.ncbi.nlm.nih.gov/books/NBK1436/).