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Blueprint Genetics Comprehensive Muscular Dystrophy / Myopathy Panel

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Blueprint Genetics Comprehensive Muscular Dystrophy / Myopathy Panel Comprehensive Muscular Dystrophy / Myopathy Panel Test code: NE0701 Is a 125 gene panel that includes assessment of non-coding variants. In addition, it also includes the maternally inherited mitochondrial genome. Is ideal for patients with distal myopathy or a clinical suspicion of muscular dystrophy. Includes the smaller Nemaline Myopathy Panel, LGMD and Congenital Muscular Dystrophy Panel, Emery-Dreifuss Muscular Dystrophy Panel and Collagen Type VI-Related Disorders Panel. About Comprehensive Muscular Dystrophy / Myopathy Muscular dystrophies and myopathies are a complex group of neuromuscular or musculoskeletal disorders that typically result in progressive muscle weakness. The age of onset, affected muscle groups and additional symptoms depend on the type of the disease. Limb girdle muscular dystrophy (LGMD) is a group of disorders with atrophy and weakness of proximal limb girdle muscles, typically sparing the heart and bulbar muscles. However, cardiac and respiratory impairment may be observed in certain forms of LGMD. In congenital muscular dystrophy (CMD), the onset of muscle weakness typically presents in the newborn period or early infancy. Clinical severity, age of onset, and disease progression are highly variable among the different forms of LGMD/CMD. Phenotypes overlap both within CMD subtypes and among the congenital muscular dystrophies, congenital myopathies, and LGMDs. Emery-Dreifuss muscular dystrophy (EDMD) is a condition that affects mainly skeletal muscle and heart. Usually it presents in early childhood with contractures, which restrict the movement of certain joints – most often elbows, ankles, and neck. Most patients also experience slowly progressive muscle weakness and wasting, beginning with the upper arm and lower leg muscles and progressing to shoulders and hips. Almost all patients with EDMD have cardiac involvement by adulthood. It presents clinically as cardiac conduction defects and/or arrhythmias. The cardiomyopathy phenotype is usually classified as dilated cardiomyopathy (DCM) but also ARVC and hypertrophic cardiomyopathies (HCM) have been described. A small proportion of patients with autosomal dominant EDMD experience cardiac manifestation without any skeletal muscle weakness or wasting. Dystrophinopathies include a spectrum of muscle diseases ranging from asymptomatic with an increase in serum concentration of creatine phosphokinase to the severe progressive muscle diseases that are classified as Duchenne or Becker muscular dystrophy (DMD or BMD) when skeletal muscle is primarily affected and as DMD-associated DCM when the heart is primarily affected. DMD usually presents in early childhood with delayed milestones, including delays in sitting and standing independently. DMD is rapidly progressive, with affected children being wheelchair dependent by age 13 years and cardiomyopathy occurring soon after that. BMD is characterized by later onset skeletal muscle weakness; some individuals remain ambulatory into their 20s. However, heart failure from DCM is a common cause of death in the mid-40s. DMD- associated DCM is characterized by left ventricular dilation and congestive heart failure. Females heterozygous for a pathogenic variant in DMD are at increased risk for DCM. The collagen type VI-related disorders are now recognized to be a continuum of overlapping phenotypes with Bethlem myopathy at the mild end and Ullrich congenital muscular dystrophy (UCMD) at the severe end. In between these phenotypes, there are collagen type VI-related limb-girdle muscular dystrophy and myosclerosis myopathy. Bethlem myopathy is characterized by proximal weakness and variable contractures. Elbows, ankles and fingers are most often affected. If the onset is in early childhood, delayed motor milestones, muscle weakness and contractures are evident. Adult onset patients require eventually ambulatory support. UCMD is characterized by congenital muscle weakness, proximal joint contractures, and striking hyperlaxity of distal joints. Affected children rarely gain the ability to walk independently and spinal rigidity and scoliosis develop. Respiratory failure is a common cause of death in the first and second decade of life. Intelligence is normal in both Bethlem myopathy and UCMD. Nemaline Myopathy is characterized by weakness, hypotonia, and depressed or absent deep tendon reflexes. Histopathologically, nemaline bodies are detected on muscle biopsy. The clinical classification defines six forms of Nemaline Myopathy, which are classified by onset and severity of motor and respiratory involvement. Considerable overlap occurs among the forms. https://blueprintgenetics.com/ Availability 4 weeks Gene Set Description Genes in the Comprehensive Muscular Dystrophy / Myopathy Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ACTA1 Myopathy AD/AR 68 212 ANO5 Gnathodiaphyseal dysplasia, LGMD2L and distal MMD3 muscular AD/AR 64 121 dystrophies ATP2A1 Brody myopathy AR 19 18 B3GALNT2 Muscular dystrophy-dystroglycanopathy AR 18 14 BAG3 Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD 39 62 BICD2 Childhood-onset proximal spinal muscular atrophy with contractures AD 12 28 BIN1 Myopathy, centronuclear AD/AR 9 15 CAPN3 Muscular dystrophy, limb-girdle, Eosinophilic myositis AD/AR 184 437 CAV3 Creatine phosphokinase, elevated serum, Hypertrophic AD/AR 23 50 cardiomyopathy (HCM), Long QT syndrome, Muscular dystrophy, limb- girdle, type IC, Myopathy, distal, Tateyama type, Rippling muscle disease 2 CFL2 Nemaline myopathy AR 2 9 CHKB Muscular dystrophy, congenital, megaconial AR 11 27 CNTN1 Myopathy, congenital, Compton-North AR 5 2 COL12A1 Bethlem myopathy, Ullrich congenital muscular dystrophy AD/AR 14 13 COL4A1 Schizencephaly, Anterior segment dysgenesis with cerebral AD 58 107 involvement, Retinal artery tortuosity, Porencephaly, Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, Brain small vessel disease COL4A2 Hemorrhage, intracerebral AD 14 12 COL6A1 Bethlem myopathy, Ullrich congenital muscular dystrophy AD/AR 81 132 COL6A2 Epilepsy, progressive myoclonic, Bethlem myopathy, Myosclerosis, AD/AR 101 182 congenital, Ullrich congenital muscular dystrophy COL6A3 Bethlem myopathy, Dystonia, Ullrich congenital muscular dystrophy AD/AR 68 138 CRYAB Cataract, myofibrillar myopathy and cardiomyopathy, Congenital AD 14 28 cataract and cardiomyopathy, Dilated cardiomyopathy (DCM), Myopathy, myofibrillar, Cataract 16, multiple types, Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related https://blueprintgenetics.com/ DES Dilated cardiomyopathy (DCM), Myopathy, myofibrillar, AD/AR 64 124 Scapuloperoneal syndrome, neurogenic, Kaeser type DMD Becker muscular dystrophy, Duchenne muscular dystrophy, Dilated XL 832 3915 cardiomyopathy (DCM) DNAJB6 Muscular dystrophy, limb-girdle AD 11 17 DYSF Miyoshi muscular dystrophy, Muscular dystrophy, limb-girdle, AR 244 529 Myopathy, distal, with anterior tibial onset EMD Emery-Dreifuss muscular dystrophy XL 48 113 FDX1L Myopathy AR 1 2 FHL1* Myopathy with postural muscle atrophy, Emery-Dreifuss muscular XL 26 62 dystrophy, Reducing bod myopathy FKRP Muscular dystrophy-dystroglycanopathy AR 66 140 FKTN Muscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy AD/AR 45 58 (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle) FLNC* Myopathy AD 54 109 GAA Glycogen storage disease AR 193 573 GMPPB Muscular dystrophy-dystroglycanopathy (congenital with brain and eye AR 19 41 anomalies), Limb-girdle muscular dystrophy-dystroglycanopathy GOLGA2 Microcephaly, seizures, and developmental delay AR 2 INPP5K Muscular dystrophy, congenital, with cataracts and intellectual AR 8 10 disability (MDCCAID) ISPD Muscular dystrophy-dystroglycanopathy AR 38 53 ITGA7 Muscular dystrophy, congenital, due to integrin alpha-7 deficiency AR 16 8 KBTBD13 Nemaline myopathy AD 4 10 KLHL40 Nemaline myopathy AR 11 26 KLHL41 Nemaline myopathy AR 8 8 LAMA2 Muscular dystrophy, congenital merosin-deficient AR 199 301 LARGE Muscular dystrophy-dystroglycanopathy AR 19 27 LDB3 Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD 9 14 LIMS2 Muscular dystrophy, limb-girdle AR 2 3 LMNA Heart-hand syndrome, Slovenian, Limb-girdle muscular dystrophy, AD/AR 250 564 Muscular dystrophy, congenital, LMNA-related, Lipodystrophy (Dunnigan), Emery-Dreiffus muscular dystrophy, Malouf syndrome, Dilated cardiomyopathy (DCM), Mandibuloacral dysplasia type A, Progeria Hutchinson-Gilford type LMOD3 Severe congenital nemaline myopathy, Typical nemaline myopathy AR 8 15 https://blueprintgenetics.com/ MAP3K20 Centronuclear myopathy AR 5 7 MEGF10 Myopathy, early-onset, areflexia, respiratory distress, and dysphagia AR 20 19 MICU1 Myopathy with extrapyramidal signs AR 10 8 MME Spinocerebellar ataxia 43, Charcot-Marie-Tooth disease, axonal, type AD/AR 14 21 2T MT-ATP6 Neuropathy, ataxia, and retinitis pigmentosa, Leber hereditary optic Mitochondrial 19 neuropathy, Ataxia and polyneuropathy, adult-onset, Cardiomyopathy, infantile hypertrophic, Leigh syndrome, Striatonigral degeneration, infantile, mitochondrial MT-ATP8 Cardiomyopathy, apical hypertrophic, and neuropathy, Mitochondrial 4 Cardiomyopathy, infantile hypertrophic MT-CO1 Myoglobinuria, recurrent, Leber hereditary optic neuropathy, Mitochondrial 17 Sideroblastic anemia, Cytochrome C oxidase deficiency MT-CO2 Cytochrome c oxidase deficiency Mitochondrial 8 MT-CO3 Cytochrome c oxidase deficiency, Leber hereditary optic neuropathy Mitochondrial 9 MT-CYB Mitochondrial 69 MT-ND1 Mitochondrial myopathy,
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