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Nemaline Myopathy via the NEB Gene, Exons 82-105 (Triplicate Repeat Region)

Summary and Pricing

Test Method

Bi-Directional Sanger Sequencing
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
2079 NEB 81479 81479 $1440 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
2079NEB81479 81479 $1440 Order Options and Pricing

Pricing Comments

CNV detection may be ordered through Test #600.

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

Turnaround Time

12 days on average for standard orders or 8 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.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Pathogenic variants in the nebulin gene (NEB) are the most common cause of autosomal recessive nemaline myopathy (NEM). 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. 2001). The most severely affected muscle groups are proximal limb, 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. 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 2002). 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. 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

All reported cases of NEB-associated NEM demonstrate autosomal recessive inheritance (Lehtokari et al. 2006; Lehtokari et al. 2014). In the largest cohort published to date, Lehtokari et al. (2014) identified 212 NEB variants segregating with autosomal recessive NEM in 159 families. In this study, pathogenic variants were found in most exons of the NEB gene, including the triplicate repeat region (exons 82-105). The majority of these variants (Lehtokari et al. 2014) were splice site variants (34%), frameshift variants (32%), and nonsense variants (23%). Reported pathogenic missense variants appear to be less common (~7%). The only common NEB pathogenic variant is an exon 55 deletion found at a carrier frequency of about 1% among people of Ashkenazi Jewish ancestry (Anderson et. al. 2004).

Clinical Sensitivity - Sanger Sequencing

The clinical sensitivity of testing this region is not known due to the complexities of analysis. To date, at PreventionGenetics we have detected at least 13 likely pathogenic or pathogenic (nonsense, slicing, and small deletions/duplications, frameshift) variants in this region. 

Testing Strategy

Exons 82-105 of the NEB gene are organized in three highly homologous blocks of 8 exons each making this region difficult to analyze by NextGen Sequencing. Due to the homology, there are mapping and alignment issues which may cause variants in this region to go undetected. We employ a novel long-range 2-step PCR with Sanger sequencing to analyze this region of the NEB gene which allows correct exon and zygosity assignment.

Indications for Test

Individuals with symptoms consistent with the typical congenital form of nemaline myopathy who may have only identified one other pathogenic NEB variant through NGS testing.

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

Related Test

Name
Nemaline Myopathy via the NEB Exon 55 Deletion

Citations

  • Anderson S.L. et al. 2004. Human Genetics. 115: 185-90. PubMed ID: 15221447
  • Lehtokari V.L. et al. 2006. Human Mutation. 27: 946-56. PubMed ID: 16917880
  • Lehtokari V.L. et al. 2014. Human Mutation. 35: 1418-26. PubMed ID: 25205138
  • North K., Ryan M.M. 2002. Nemaline Myopathy. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301465
  • Ryan M.M. et al. 2001. Annals of Neurology. 50: 312-20. PubMed ID: 11558787
  • Ryan M.M. et al. 2003. Neurology. 60: 665-73. PubMed ID: 12601110

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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