Nemaline Myopathy Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10283 ACTA1 81479,81479 Order Options and Pricing
CFL2 81479,81479
KBTBD13 81479,81479
KLHL40 81479,81479
KLHL41 81479,81479
LMOD3 81479,81479
NEB 81408,81479
TNNT1 81479,81479
TPM2 81479,81479
TPM3 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10283Genes x (10)81479 81408, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Nemaline myopathy (NM) 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, NM 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 NM have been delineated based on age of onset, severity and distribution of weakness, and respiratory function (Ryan et al. 2001; North and Ryan. 2015). Overlap among the six clinical groups is significant and adults are sometimes diagnosed only after another family member has presented with typical signs. Nebulin gene pathogenic variants most often cause typical neonatal onset disease, although NEB pathogenic variants have been found in every clinical form of NM (Lehtokari et al. 2006). Troponin T1 associated NM is a lethal disorder described only in the Old Order Amish community of Pennsylvania (Johnston et al. 2000). Nemaline myopathy-8 due to pathogenic variants in the KLHL40 gene represents a severe form of this disease with features of fetal akinesia or hyopkinesia and early lethality (Ravenscroft et al. 2013).

Genetics

Pathogenic variants in a growing number of genes have been shown to cause nemaline myopathy. Most forms of nemaline myopathy (NEB, CFL2, KLHL40, KLHL41, LMOD3 and TNNT1) are inherited as autosomal recessive diseases, although ACTA1 or TPM3-related nemaline myopathy can be inherited as a dominant or recessive condition. TPM2 and KBTBD13-related nemaline myopathy are inherited as autosomal dominant conditions (Nowak et al 2015). Pathogenic variants in NEB and ACTA1 are the only relatively common causes accounting for up to 50% and 15-25%, respectively, of all studied cases (Ryan et al. 2001; North and Ryan 2015). The majority of reported NEB pathogenic variants (Lehtokari et al. 2014) are splice site variants (34%), frameshift (32%), and nonsense (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). ACTA1 missense variants are a major type of reported dominant pathogenic variants and are commonly associated with sporadic (de novo) cases. Recessive ACTA1-related myopathy is very rare, usually due to null ACTA1 pathogenic variants, in the compound heterozygous state with pathogenic missense variants (Laing et al. 2009; http://www.LOVD.nl/ACTA1). See individual gene test descriptions for information on molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

Nebulin gene pathogenic variants are most common cause of Nemaline Myopathy, accounting for up to 50% of cases (Ryan et al. 2001; North and Ryan 2002). ACTA1 pathogenic variants account for 15%-25% of all individuals with NM (Laing et al. 2009). Eight other genes (TPM3, TNNT1, TPM2, CFL2, LMOD3, KBTBD13, KLHL40, KLHL41) are involved with NM, however, the fraction of cases attributed to each of them is small. Deletion of exon 55 of NEB occurs with a carrier frequency of ~1% among people of Ashkenazi Jewish ancestry (Anderson et al. 2004).

Clinical sensitivity for deletion/duplication testing is expected to be low. One exception is the Ashkenazi Jewish nebulin exon 55 deletion.

Testing Strategy

This panel typically provides ≥98% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

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 only and are not included in this test.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Individuals with clinical symptoms consistent with nemaline myopathy and a muscle biopsy with nemaline bodies.

Genes

Official Gene Symbol OMIM ID
ACTA1 102610
CFL2 601443
KBTBD13 613727
KLHL40 615340
KLHL41 607701
LMOD3 616112
NEB 161650
TNNT1 191041
TPM2 190990
TPM3 191030
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Anderson S.L. et al. 2004. Human Genetics. 115: 185-90. PubMed ID: 15221447
  • Johnston J.J. et al. 2000. American Journal of Human Genetics. 67: 814-21. PubMed ID: 10952871
  • Laing N.G. et al. 2009. Human Mutation. 30: 1267-77. PubMed ID: 19562689
  • 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
  • Leiden Muscular Dystrophy Pages- ACTA1
  • North K, Ryan MM. 2015. 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
  • Nowak K.J. et al. 2015. European Journal of Human Genetics. 0: N/A. PubMed ID: 25712079
  • Ravenscroft G. et al. 2013. American Journal of Human Genetics. 93: 6-18. PubMed ID: 23746549
  • 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.

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

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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.

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