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Expanded Neuromuscular Disorders

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Condition Description  Detection
Indications Specimen Requirements

 

Condition Description            

 Neuromuscular disorders (NMDs) collectively refer to the many disorders that affect the peripheral nervous system either by impairing the proper development or functioning of muscles, or by damaging the associated nerves or neuromuscular junctions. NMDs comprise over 200 Mendelian disorders, all of which are rare individually, but have an approximate disease prevalence of 1 in 3,000 altogether. Of the inherited NMDs, muscular dystrophies are the most common. Muscular dystrophies are highly heterogeneous muscle disorders that share clinical, genetic, and pathological characteristics; their major clinical characteristics include muscle degeneration and wasting, progressive muscle weakness, hypotonia, and elevated serum creatine kinase levels.

 The expanded neuromuscular panel includes a wide range of clinical presentation and heterogeneity. They include muscular dystrophies, congenital myopathies, and congenital myasthenic syndrome. Over the past few years a number of genes with overlapping clinical phenotypes have been identified in neuro muscular disorders. The expanded neuro muscular disorders panel is designed to capture the entire mutation spectrum of these genes.

Genes                                                                                                                                                                       

 ACTA1, AMPD1, ANO5, BAG3, BIN1, BSCL2, CAPN3, CAV3, CFL2, CHAT, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, COL6A1, COL6A2, COL6A3, COLQ, CRYAB, DAG1, DES, DMD, DNM2, DOK7, DYSF, EMD, FHL1, FKRP, FKTN, FLNC, GAA, GLE1, GNE, IGHMBP2, ISPD, ITGA7, LAMA2, LARGE, LDB3, LMNA, MTM1, MTMR14, MUSK, MYH2, MYH7, MYOT, NEB, PABPN1, PLEC, PLEKHG5, PMM2, POMGNT1, POMT1, POMT2, PTRF, PYGM, RAPSN, RYR1, RYR2, SCN4A, SEPN1, SGCA, SGCB, SGCD, SGCE, SGCG, SIL1, SYNE1, SYNE2, TCAP, TNNI2, TNNT1, TPM2, TPM3, TRIM32, TTN, VCP, VRK1

Indications                                                                                                                                                             

 This test is indicated for:

 Confirmation of a clinical diagnosis of neuromuscular disorders.

Methodology                                                                                                                                                           

 Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient's genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient's gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

Detection                                                                                                                                                                 

 Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of  the patient's clinical/biochemical phenotype.

 Analytical Sensitivity:~99%.

Specimen Requirements                                                                                                                                          

 Submit only 1 of the following specimen types

Type: Whole Blood

Specimen Requirements:

 In EDTA (purple top) tube: Infants (2 years): 3-5 ml

 Older Children & Adults: 5-10 ml.

 Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.

Type: Isolated DNA

 Specimen Requirements: In microtainer: 60ug

 Isolation using the QiagenTM  Puregene kit for DNA extraction is recommended.

 Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.