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Limb Girdle Muscular Dystrophy Type 2I via the FKRP Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7649 FKRP 81404 81404,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7649FKRP81404 81404,81479 $990 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

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

Variants in FKRP cause muscular dystrophies in the dystroglycanopathy spectrum. Limb girdle muscular dystrophy type 2I (LGMD2I, OMIM 607155; Brockington et al. Hum. Molec. Genet. 10:2851-2859, 2001) is often associated with a European founder variant (c.826C>A, p.Leu276Ile) and homozygotes for this variant often have mild weakness, elevated serum CK levels, and no CNS involvement. Other variants in FKRP are known to cause congenital muscular dystrophy (CMD), the most severe form of which is indistinguishable from Walker-Warburg syndrome (WWS, OMIM 236670; Beltran-Valero de Bernabe et al. J. Med. Genet. 41: e61, 2004). Patients with WWS typically die at birth or shortly thereafter due to complications from severe CNS structural abnormalities. Other patients with FKRP variants have a phenotype intermediate between LGMD2I and WWS designated MDC1C (OMIM 606612; Brockington et al. Am. J. Hum. Genet. 69: 1198-1209, 2001). Patients with MDC1C have weakness both distally and proximally and contractures of knee, elbow, and finger joints are observed. Other findings include occasional cardiomyopathy, respiratory failure, calf and quadriceps hypertrophy, and macroglossia.

Genetics

FKRP-related disorders are inherited in an autosomal recessive manner. Disease-causing variants of all forms are found throughout exon 4, but the European founder variant is found on roughly 80% of all LGMD2I chromosomes (see for example Moore et al. J Neuropathol Exp Neurol 65:995-1003, 2006). Variants in FKRP lead to reduced glycosylation of alpha-dystroglycan (ADG), a component of the dystrophin-glycoprotein complex (Ervasti et al. Nature 345:315-319, 1990). Evaluation of a patient’s muscle biopsy by immunofluorescence can detect abnormal glycosylation of ADG and can, therefore, help direct a diagnostic evaluation. It should be noted that at least six other genes (POMT1, POMT2, ISPD, POMGNT1, FKTN, and LARGE) encode proteins required for processing of ADG, and overlap exists between clinical phenotypes resulting from variants in these genes.

Clinical Sensitivity - Sequencing with CNV PG-Select

Because LGMD and CMD both demonstrate extensive locus and allelic heterogeneity (Moore et al., J. Neuropathol. Exp. Neurol. 65:995-1002), a negative FKRP sequence result does not rule out a diagnosis of LGMD2I, MDC1C, or WWS when classic clinical findings are present. If a muscle biopsy is available, immunostaining may also be an appropriate diagnostic approach.

Testing Strategy

This test provides full coverage of all coding exons of the FKRP gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with symptoms consistent with LGMD or CMD. Individuals with immunofluorescence results demonstrating hypoglycosylation of ADG in muscle. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in FKRP.

Gene

Official Gene Symbol OMIM ID
FKRP 606596
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Comprehensive Cardiology Panel

Citations

  • Beltran-Valero de Bernabe, D., et.al. (2004). "Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome." J Med Genet 41(5): e61. PubMed ID: 15121789
  • Brockington, M., et.al. (2001). "Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha2 deficiency and abnormal glycosylation of alpha-dystroglycan." Am J Hum Genet 69(6): 1198-209. PubMed ID: 11592034
  • Brockington, M., et.al. (2001). "Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C." Hum Mol Genet 10(25): 2851-9. PubMed ID: 11741828
  • Ervasti, J. M., et.al. (1990). "Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle." Nature 345(6273): 315-9. PubMed ID: 2188135
  • 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

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

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ORDER OPTIONS

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View Ordering Instructions

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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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