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Distal Myopathy via the KLHL9 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
10497 KLHL9 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10497KLHL981479 81479,81479 $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.

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 backbone).

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

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

The hereditary distal myopathies are a genetically and clinically heterogeneous group of disorders characterized by prominent weakness beginning in the anterior or posterior compartment of either the distal upper or the distal lower limbs. Weakness of the wrists and ankles is a common pattern of muscle involvement. Age of onset, disease severity, rate of progression, and muscle pathology all vary among the many genetic subtypes of this disorder. For example, patients with Laing myopathy may present as early as 4 years of age (Meredith et. al. 2004. PubMed ID: 15322983), while patients affected by Udd myopathy or Welander myopathy may not become clinically affected until the 5th decade of life (Udd et al. 1993. PubMed ID: 8503797; Klar et al. 2013. PubMed ID: 23348830). Serum CpK levels are typically normal or slightly elevated; however, patients with Miyoshi myopathy, Miyoshi-like myopathy, and TCAP related myopathy have CpK levels 100-fold elevated over normal. Muscle pathology of the distal myopathies often reveal varied fiber size and abnormal vacuoles, and those subtypes with myofibrillar changes show accumulation of desmin. A diagnostic algorithm for the distal myopathies using clinical and laboratory data has been proposed (Udd. 2009. PubMed ID: 19477645). For a recent review of distal myopathies see Dimachkie and Barohn 2014 (Dimachkie and Barohn. 2014. PubMed ID: 25037092).

Distal myopathy due to a pathogenic KLHL9 variant was first described in a large 4 generation German family in which linkage analysis and candidate gene sequencing were used to discover the causative KLHL9 gene (Cirak et al. 2010. PubMed ID: 20554658). Onset was between the ages of 8 and 16 years. Typical symptoms included difficulty walking on heels followed by slow wasting of ankle extensors, high steppage gait, ankle contractures, and weakness in intrinsic hand muscles. The progression was slow and proximal muscle groups were spared.

Genetics

Distal myopathy due to KLHL9 pathogenic variants is inherited in an autosomal dominant manner. The KLHL9 gene encodes Kelch-like homologue 9 (KLHL9) which binds to Cul3 to form an E3 ubiquitin ligase complex. The KLHL9-Cul3-Roc1 E3 ubiquitin ligase complex ubiqintinates substrate proteins for degradation by the proteasome. Thus far, the only established pathogenic variant reported in one large German family is a missense variant referred to as c.283C>T p.Leu95Phe, which was shown to result in reduced binding to Cul3 (Cirak et al. 2010. PubMed ID: 20554658; Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of patients have been reported. However, pathogenic variants in KLHL9 appear to be a rare cause of disease. Analytical sensitivity should be high because all reported pathogenic variants thus far are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the KLHL9 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 clinical symptoms consistent distal myopathy and autosomal dominant inheritance. Testing is also indicated for family members of patients who have known KLHL9 pathogenic variants.

Gene

Official Gene Symbol OMIM ID
KLHL9 611201
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID

Citations

  • Cirak et al. 2010. PubMed ID: 20554658
  • Dimachkie and Barohn. 2014. PubMed ID: 25037092
  • Human Gene Mutation Database (Bio-base).
  • Klar et al. 2013. PubMed ID: 23348830
  • Meredith et.al. 2004. PubMed ID: 15322983
  • Udd et al. 1993. PubMed ID: 8503797
  • Udd. 2009. PubMed ID: 19477645

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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.
Total Price: $
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