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Autosomal Dominant Limb-Girdle Muscular Dystrophy, Type 1E (LGMD1E) via the DNAJB6 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
11247 DNAJB6 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11247DNAJB681479 81479,81479 $990 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. If the Sanger option is selected, 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.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

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

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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

Limb-girdle muscular dystrophy (LGMD) is a descriptive term for a group of disorders with atrophy and weakness of proximal limb-girdle muscles. At least ten genes are recognized as causative for autosomal recessive LGMD (AR-LGMD), which is overall more common than autosomal dominant LGMD (AD-LGMD, Moore et al. J Neuropath Exp Neurol 65:995-1003, 2006). To date, four genes have been reported to be causative for AD-LGMD (see Genetics Section below and Gordon et al. GeneReviews, 2009). LGMD1E (OMIM 603511) is an adult-onset disorder of proximal weakness first presenting in the hip girdle. The age of onset has been reported to range from 20 to 60 years (Sandell et al. J Neurol Neurosurg Psychiat 81:834-839, 2010) and 18 to 35 years (Harms et al. Ann Neurol 71:407-416, 2012) in two affected families. Difficulty climbing stairs is a common presenting symptom. Disease progression is slow and shoulder girdles are eventually also affected. By the 8th decade of life, independent ambulation may be limited (Sandell et al. 2010; Hackman et al. Neuromusc Disord 21:338-344, 2011). Facial weakness and pulmonary and cardiac involvement are not features of LGMD1E. Dysphagia appears to be a variable finding. Serum CpK values are elevated, and EMG studies reveal myopathic changes. Muscle biopsies are remarkable for a dystrophic process including fiber size variation, atrophic fibers, mild to moderate fibrosis, adipose tissue, rimmed vacuoles, and internally placed nuclei (Sandell et al. 2010). Cytoplasmic inclusions that contain DNAJB6 protein are present. Electron microscopy of affected muscle reveals Z-disc myofibrillar disintegration and autophagic rimmed vacuoles (Sarparanta et al. Nature Genet 44: 450-455, 2012).

Genetics

LGMD1A, 1B, 1C, and 1E are inherited as autosomal dominant disorders secondary to variants in the MYOT, LMNA, CAV3, and DNAJB6 genes, respectively. Thus far four different DNAJB6 variants (p.Phe89Ile, p.Phe93Gly, p.Phe93Leu, p.Pro96Arg) have been reported (Harms et al. 2012 and Sarparanta et al. 2012). These variants extend the half-life of the DNAJB6 protein and lead to a toxic gain-of-function effect (Sarparanta et al. 2012).

The DNAJB6 protein is coded by exons 2-10 of the DNAJB6 gene (OMIM 611332) located on chromosome 7q36.3.

Clinical Sensitivity - Sequencing with CNV PGxome

LGMD1E is a rare disorder and most affected families reported have been from Finland. Clinical sensitivity cannot be accurately predicted because of the low rate of occurrence of this disorder. Analytical sensitivity may be high because all variants thus far reported are expected to be detected by this method.

Testing Strategy

This test provides full coverage of all coding exons of the DNAJB6 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Individuals with adult onset limb-girdle weakness presenting in the hip girdle and slowly progressing to the shoulder girdle.

Gene

Official Gene Symbol OMIM ID
DNAJB6 611332
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Erynn Gordon, et.al. (2009). "Limb-Girdle Muscular Dystrophy Overview."
  • Hackman et al. Neuromusc Disord 21:338-344, 2011 PubMed ID: 21376592
  • Harms et al. Ann Neurol 71:407-416, 2012 PubMed ID: 22334415
  • Moore SA, Shilling CJ, Westra S, Wall C, Wicklund MP, Stolle C, Brown CA, Michele DE, Piccolo F, Winder TL, Stence A, Barresi R, King N, King W, Florence J, Campbell KP, Fenichel GM, Stedman HH, Kissel JT, Griggs RC, Pandya S, Mathews KD, Pestronk A, Serrano C, Darvish D, Mendell JR. 2006. Limb-girdle muscular dystrophy in the United States. J Neuropathol Exp Neurol 65: 995-1003. PubMed ID: 17021404
  • Sandell et al. J Neurol Neurosurg Psychiat 81:834-839, 2010 PubMed ID: 20682716
  • Sarparanta et al. Nature Genet 44: 450-455, 2012 PubMed ID: 22366786

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


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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.

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