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Nemaline Myopathy via the NEB Exon 55 Deletion

Summary and Pricing

Test Method

Targeted Deletion Testing via PCR
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
356 NEB 81400 81400 $250 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
356NEB81400 81400 $250 Order Options and Pricing

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Variants in the nebulin gene (NEB, OMIM 161650) are one cause of autosomal recessive nemaline myopathy (NEM, OMIM 256030). NEM is a genetically and clinically heterogeneous disorder characterized by muscle weakness, hypotonia and the presence of nemaline bodies in skeletal muscle fibers. Muscle weakness is typically observed in affected neonates or infants, although later onset cases are reported (Ryan et al. Ann Neurol 50:312-320, 2001). The most severely affected muscle groups are proximal limb muscles, facial, bulbar, and respiratory muscles. Deep tendon reflexes are absent or depressed. Histologically, NEM is characterized by type 1 fiber predominance and the presence of rod-like structures called nemaline bodies upon Gomori trichrome staining of skeletal muscle (Ryan et al. Neurol 60:665-673, 2003). Six clinical types of NEM have been delineated based on age of onset, severity and distribution of weakness, and respiratory function (Ryan et al. 2001; North and Ryan. GeneReviews 2010). Nebulin gene variants more often cause typical neonatal-onset disease, although NEB variants have been found in every clinical form of NEM (Lehtokari et al. Hum Mut 27:946-956, 2006). Overlap among the six clinical groups is significant, and adults are sometimes diagnosed only after another family member has presented with typical signs.

Genetics

To date, variants in six genes have been shown to cause nemaline myopathy. Variants in ACTA1 (NEM3) and NEB (NEM2) are the only relatively common causes (Ryan et al. 2001). All reported cases of NEB-associated NEM have demonstrated autosomal recessive inheritance (Lehtokari et al. 2006). The only common NEB variant is an exon 55 deletion found at a carrier frequency of about 1% among people of Ashkenazi Jewish ancestry (Anderson et al. Hum Genet 115:185-190, 2004). Much rarer causes of NEM are variants in TPM3 (NEM1), TPM2 (NEM4), TNNT1 (NEM5), and CFL2 (NEM7).

Clinical Sensitivity - Targeted Deletion

This test is intended to detect the exon 55 NEB deletion variant found in Ashkenazi Jews; it will not detect any other sequence variant.  In a world-wide cohort of 355 patients with nemaline myopathy, fourteen probands were found to have the exon 55 deletion variant and all shared the same ancestral haplotype (Lehtokari et al. Neuromusc Disord 19:179-181, 2009).  Sequencing the entire NEB coding region may be indicated in individuals who are clinically affected and have either one or no alleles with the exon 55 deletion.  Complete NEB gene sequencing is available from PreventionGenetics.  Because nemaline myopathy exhibits locus and allelic heterogeneity, a negative NEB test does not rule out this diagnosis when classic clinical and histological findings are present.

Testing Strategy

Testing is accomplished by amplifying patient and control DNAs with PCR primers that flank or lie within the 2,502 bp deletion, essentially as described by Anderson et al. (Hum Genet 115:185-190, 2004). This test permits the identification of patients with normal genotypes, patients who are homozygous for the deletion, and heterozygous carriers.

Indications for Test

Individuals of Ashkenazi Jewish ancestry with symptoms consistent with nemaline myopathy whose muscle biopsies show predominance of type 1 fibers and nemaline bodies.

Gene

Official Gene Symbol OMIM ID
NEB 161650
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Nemaline Myopathy 2 AR 256030

Citations

  • Anderson SL, Ekstein J, Donnelly MC, Keefe EM, Toto NR, LeVoci LA, Rubin BY. 2004. Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene. Hum Genet 115: 185-190. PubMed ID: 15221447
  • Kathryn North, Monique M Ryan (2010). "Nemaline Myopathy."
  • Lehtokari VL, Pelin K, Sandbacka M, Ranta S, Donner K, Muntoni F, Sewry C, Angelini C, Bushby K, Van den Bergh P, Iannaccone S, Laing NG, Wallgren-Pettersson C. 2006. Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Hum Mutat 27: 946-956. PubMed ID: 16917880
  • Ryan MM, Ilkovski B, Strickland CD, Schnell C, Sanoudou D, Midgett C, Houston R, Muirhead D, Dennett X, Shield LK, Girolami U De, Iannaccone ST, Laing NG, North KN, Beggs AH. 2003. Clinical course correlates poorly with muscle pathology in nemaline myopathy. Neurology 60: 665–673. PubMed ID: 12601110
  • Ryan MM, Schnell C, Strickland CD, Shield LK, Morgan G, Iannaccone ST, Laing NG, Beggs AH, North KN. 2001. Nemaline myopathy: a clinical study of 143 cases. Ann. Neurol. 50: 312–320. PubMed ID: 11558787

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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