• Test Code:
    1575
  • Department:
    Molecular Genetics
  • Test Synonyms:
    Neuromuscular disordersCongenital muscular dystrophyEmery-Dreifuss muscular dystrophyLimb-Girdle muscular dystrophyACTA1AMPD1ANO5BAG3BIN1BSCL2CAPN3CAV3CFL2CHATCHRNA1CHRNB1CHRNDCHRNECHRNGCOL6A1COL6A2COL6A3COLQCRYABDAG1DES DMDDNM2DOK7DYSFEMDFHL1FKRPFKTNFLNCGAAGLE1GNEIGHMBP2ISPDITGA7LAMA2LARGELDB3LMNAMTM1MTMR14MUSKMYH2MYH7MYOTNEBPABPN1PLECPLEKHG5 PMM2POMGNT1POMT1POMT2PTRFPYGMRAPSNRYR1RYR2SCN4ASEPN1SGCASGCBSGCDSGCESGCGSIL1SYNE1SYNE2TCAPTNNI2TNNT1TPM2TPM3TRIM32TTNVCPVRK1
  • CPT Code(s):
    81408
Background:

Neuromuscular disorders are a group of heterogeneous conditions affecting the nervous system that controls muscle movements. This neuronal damage in turn causes degradation of the affected muscular tissue causing weakness and loss of muscle tone. This comprehensive test includes muscular dystrophies, congenital muscular dystrophy, nemaline myopathy, Emery-Dreifuss muscular dystrophy, and Limb-Girdle muscular dystrophy, and syndromic conditions where the phenotype includes neuromuscular disorders. Clinical presentation can be variable but include cardiomyopathies, muscle weakness and abnormalities in serum creatine kinase, electromyography, positive muscle biopsies and nerve conduction studies. The inheritance patterns for neuromuscular disorders can follow autosomal dominant, recessive and X-linked. This test combines both next-generation sequencing and exon level deletion-duplication analysis for these 79 genes.

Reasons for Referral:

  • Abnormal serum creatine kinase levels
  • Abnormal electromyography (EMG)
  • Abnormal nerve conduction studies (NCS)
  • Positive family history (targeted testing is available if familial mutation is known).
  • Carrier testing.

Methodology:

This test has two components:

Component 1: Next generation sequencing will analyze the exons or coding regions of 79 neuromuscular disorder genes using Illumina NextSeq 500 technology and preparing samples using hybridization probes to enrich exonic regions. Promoter, intronic, etc. regions are not assessed here but may contain variants that impact gene function. Additionally, the assay does not assess coding regions with incomplete coverage some of which including regions of high homology (pseudogenes), regions of high GC content and polynucleotide repeats.

Coding region coverage for the Comprehensive Neuromuscular panel genes

Coding region coverage for the Comprehensive Neuromuscular panel genes

Gene Name

Gene Coverage

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

95%-100%

ISPD, MUSK, PTRF,

90%-95%

DES, FKRP, NEB, PABPN1, SEPN1,

75%-90%

Coding regions below 95% may be covered upon request if further assessment of a gene is necessary (some exceptions may apply). Please contact Knight Diagnostic Laboratories for more information.

Component 2: Microarray Analysis – A customized CytoSure “exon-centric” array (Oxford Gene Technology) will be used to detect deletions and duplications. The targeted array has enhanced probes targeted to the exonic regions of the 79 neuromuscular disorder genes. The arrays will be run using Agilent SureScan technology. This array is an ideal complement to the next generation sequencing approach to provide a comprehensive mutation spectrum analysis for neuromuscular disorders.

Related Tests:
Knight Diagnostic Laboratories also offers smaller, focused panels:

Specimen Requirements:

Blood:  EDTA or ACD (Solution A or B):

  • Adult: 5 mL
  • Child: 5 mL
  • Infant: 2-3 mL

DNA: 10µg at a minimum of 60-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

8 weeks

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided.
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

  1. Journal of Muscular Diseases 2015(2):73-85

Additional Info: