Nemaline Myopathy

Nemaline myopathy (NM) is a disorder characterized by muscle weakness, depressed/absent deep tendon reflexes and the presence of rod-shaped structures in muscle cells. Clinical expression is variable and ranges from congenital muscle weakness and hypotonia to mild skeletal myopathy of childhood or adult onset. The distribution of weakness is typically proximal, with variable involvement of the facial, bulbar, and respiratory muscles. Many affected infants have feeding difficulties and about 25-40% of infants with congenital NM die, often from respiratory failure. In those who survive the first few years or those with late onset of symptoms, muscle weakness often stabilizes or is slowly progressive. Few patients display a cardiac phenotype. The majority of patients with a mutation in the NEB gene have the typical congenital form of NM. The NEB gene encodes the nebulin protein, which is a component of the skeletal muscle. Creatine kinase levels in NM are normal to mildly elevated. The incidence of NM is 1:50,000 live births, although it is higher in patients with Ashkenazi Jewish ancestry, due to a founder mutation in the NEB gene.

Tests Available

Forms and Documents

Test Details

ACTA1
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

244
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
Yes
Yes
  • 359 Muscular dystrophies and other myopathies Excludes: idiopathic polymyositis (710.4)
* For price inquiries please email zebras@genedx.com

References

  1. North KN, et al., (1997) J Med Genet. 34:705-713
  2. Ryan MM, et al., (2001) Ann Neurol. 50:312:320
  3. Anderson SL, et al., (2004) Hum Genet. 115: 185–90
  4. Agrawal PB, et al., (2004) Ann Neurol. 2004; 56: 86– 96
  5. Ilkowski B, et al., (2005) Neuromuscul Disord. 15:829:835
  6. Laing NG, et al., (2009) Hum Mutat. 30(9):1267- 77
  7. North K & Ryan C, (2010) www.genereviews.org

Forms and Documents

Test Details

ACTA1, NEB
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

551
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81400x1, 81479x1
No
Yes
  • 359 Muscular dystrophies and other myopathies Excludes: idiopathic polymyositis (710.4)
* For price inquiries please email zebras@genedx.com

References

  1. North K & Ryan C, (2010) www.genereviews.org
  2. Laing NG, et al., (2009) Hum Mutat. 30(9):1267- 77
  3. Ilkowski B, et al., (2005) Neuromuscul Disord. 15:829:835
  4. Agrawal PB, et al., (2004) Ann Neurol. 2004; 56: 86– 96
  5. Anderson SL, et al., (2004) Hum Genet. 115: 185–90
  6. Ryan MM, et al., (2001) Ann Neurol. 50:312:320
  7. North KN, et al., (1997) J Med Genet. 34:705-713
  8. Wallgren-Peterson C, et Al. (1990) Neuromusc Disord 9:564:572.
  9. Wallgren-Pettersson C et Al., (2004) Neuromuscular Disord. 14: 461-70.
  10. Ilkowski B, et Al., (2005) Neuromuscul Disord. 15:829:835.
  11. McElhinny AS, et Al., (2005) J Cell Biol 170: 947-957.
  12. Laing NG, et Al., (2009) Hum Mutat. 30(9):1267-77.
  13. Lehtokari VL et Al., (2009) Neuromuscul Disord 19(3):179-81.

Forms and Documents

Test Details

ACTA1, ANO5, ATP2A1, B3GALNT2, B3GNT1, BAG3, BICD2, BIN1, CACNA1S, CAPN3, CAV3, CFL2, CHKB, CLCN1, CNTN1, COL6A1, COL6A2, COL6A3, CRYAB, DAG1, DES, DMD, DNAJB6, DNM2, DPM1, DPM2, DPM3, DYNC1H1, DYSF, EMD, FHL1, FKRP, FKTN, FLNC, GAA, GMPPB, GNE, IGHMBP2, ISPD, ITGA7, KBTBD13, KLHL40, LAMA2, LAMP2, LARGE, LDB3, LMNA, MEGF10, MTM1, MYH7, MYOT, NEB, PHKA1, PLEC, PLEKHG5, POMGNT1, POMT1, POMT2, PYGM, RYR1, SCN4A, SEPN1, SGCA, SGCB, SGCD, SGCG, SIL1, SYNE1, TCAP, TMEM5, TNNI2, TNNT1, TNPO3, TPM2, TPM3, TRIM32, TRPV4, TTN, UBA1, VRK1
  • Molecular confirmation of a clinical diagnosis
  • Identification of at-risk family members
  • Assist with treatment/ management decisions
  • Recurrence risk assessment
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

889
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x2, 81406x4, 81407x3, 81408x3
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Agrawal, et al. (2007). Am. J. Hum. Genet. 80, 162-167.
  2. Van der Kooi, A.J., et al. (2013). Neuromuscular Disord. 23, 456-460.
  3. Mitsuhashi, S., Kang, P.B. (2012). Semin. Pediatr. Neurol. 19, 211-218.
  4. Voermans, N.C., et al. (2012). Neuromuscular Disord. 22, 944-954.
  5. Stevens, E., et al. (2013) Am. J. Hum. Genet. 92: 354-365, 2013. (PubMed: 23453667)
  6. Hayashi, Y.K. (2011). Brain Nerve 63, 1179-1188.
  7. Olivé, M., et al. (2013). Curr. Opin. Neurol. 26, 527-535.
  8. Biancalana, et al. (2012). Eur. J. Hum. Genet. 20, 1101.
  9. Statland, J.M., Barohn, R.J. (2013). CONTINUUM Lifelong Learn. Neurol. 19, 1598-1614.
  10. Jungbluth, H., Wallgren-Pettersson, C. (2013). Emery and Rimoin\\\\\\\'s Principles and Practice of Medical Genetics, 1-51.

Forms and Documents

Test Details

ACTA1, BICD2, CFL2, CHKB, COL6A1, COL6A2, COL6A3, FKRP, FKTN, ITGA7, KBTBD13, LAMA2, LMNA, MEGF10, MTM1, NEB, RYR1, SEPN1, SYNE1, TNNT1, TPM2, TPM3
  • Molecular confirmation of a clinical diagnosis
  • Identification of at-risk family members
  • Assist with management/treatment decisions
  • Recurrence risk
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

892
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x1, 81406x1, 81407x2, 81408x2
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Agrawal, et al. (2007). Am. J. Hum. Genet. 80, 162-167.
  2. Ockeloen, C.W., et al. (2012). Neuromuscular Disord. 22, 632-639.
  3. Mitsuhashi, S., Nishino, I. (2013). Curr. Opin. Neurol. 26, 536-543.
  4. Butterfield, R.J., et al. (2013). Hum. Mutat. 34, 1558-1567.
  5. Wicklund, M.P. (2013). Continuum (Minneap Minn) 19, 1535-1570.
  6. Clement, et al. (2012). Neuromuscular Disord. 22, 522-527. 7
  7. Yis, et al. (2011). Neuromuscular Disord. 21, 20-30.
  8. Anonymous Limb-Girdle Muscular Dystrophy Overview - GeneReviews® - NCBI Bookshelf, http://www.ncbi.nlm.nih.gov/books/NBK1408/.
  9. Saito, Fukuyama Congenital Muscular Dystrophy-GeneReviews® - NCBI Bookshelf, http://www.ncbi.nlm.nih.gov/books/NBK1206/.
  10. Godfrey, et al. (2011). Curr. Opin. Genet. Dev. 21, 278-285.

Forms and Documents

Test Details

NEB
  • Confirmation of clinical diagnosis
  • Determination of inheritance pattern of NM in a new Ashkenazi Jewish patient (a sporadic autosomal dominant ACTA1 mutation versus two inherited nebulin recessive mutations)
  • Carrier testing in unaffected family members
  • Recurrence risk calculation
  • Prenatal diagnosis for couples with known mutations
  • Long Range PCR

Ordering

245
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81400x1
Yes
Yes
  • 359 Muscular dystrophies and other myopathies Excludes: idiopathic polymyositis (710.4)
* For price inquiries please email zebras@genedx.com

References

  1. North K & Ryan C, (2010) www.genereviews.org
  2. Lehtokari VL et Al., (2009) Neuromuscul Disord 19(3):179-81
  3. Laing NG, et Al., (2009) Hum Mutat. 30(9):1267-77
  4. McElhinny AS, et Al., (2005) J Cell Biol 170: 947-957
  5. Ilkowski B, et Al., (2005) Neuromuscul Disord. 15:829:835
  6. Anderson S et Al., (2004) Hum Genet. 115: 185-90, 2004
  7. Agrawal PB, et Al., (2004) Ann Neurol. 2004; 56: 86–96
  8. Ryan MM, et Al., (2001) Ann Neurol. 50:312:320
  9. North KN, et Al., (1997) J Med Genet. 34:705-713
  10. Wallgren-Peterson C, et Al. (1990) Neuromusc Disord 9:564:572
  11. Wallgren-Pettersson C et Al., (2004) Neuromuscular Disord. 14: 461-70