Nemaline Myopathy 10 via the LMOD3 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11451 LMOD3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11451LMOD381479 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

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

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing 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 have been 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.

Nemaline myopathy 10 is caused by pathogenic variants in the LMOD3 gene. A severe congenital phenotype was observed in 13 of 14 families (Yuen et al. 2014). Polyhydramnios (62% of patients), decreased or absent fetal movements (48% of patients), and joint contractures (48% of patients) were also observed in this cohort of patients. All patients had severe generalized hypotonia, respiratory insufficiency, feeding difficulties, and bulbar weakness.

Genetics

Nemaline myopathy 10 is inherited in an autosomal recessive manner due to pathogenic variants in LMOD3, located on chromosome 3p14.1. The LMOD3 gene encodes for the leiomodin-3 (LMOD3) protein which has been identified as a binding partner for KLHL40 and is necessary for stability of the sarcomere thin filament. Absence of LMOD3 results in shortening and disorganization of thin filaments (Yuen et al. 2014). Pathogenic variants reported include missense, nonsense, small deletions/duplications that result in a frame-shift and premature protein truncation, and a small in-frame deletion of a single amino acid (Yuen et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

NEB gene pathogenic variants are most common cause of nemaline myopathy, accounting for up to 50% of cases (Ryan et al. 2001; North and Ryan 2015). ACTA1 pathogenic variants account for 15%-25% of all individuals with nemaline myopathy (Laing et al. 2009). Eight other genes (TPM3, TNNT1, TPM2, CFL2, LMOD3, KBTBD13, KLHL40, KLHL41) are involved with nemaline myopathy; however, the fraction of cases attributed to each of them is small (North and Ryan 2015).

Testing Strategy

This test provides full coverage of all coding exons of the LMOD3 gene 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 full coverage as >20X NGS reads or Sanger sequencing.

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. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LMOD3.

Gene

Official Gene Symbol OMIM ID
LMOD3 616112
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Nemaline Myopathy 10 AR 616165

Citations

  • Laing N.G. et al. 2009. Human Mutation. 30: 1267-77. PubMed ID: 19562689
  • North K., Ryan M.M. 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
  • 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
  • Yuen M. et al. 2014. The Journal of Clinical Investigation. 124: 4693-708. PubMed ID: 25250574

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

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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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