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Dystroglycanopathy via the FKTN 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
7651 FKTN 81405 81405,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7651FKTN81405 81405,81479 $640 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.

Turnaround Time

18 days on average for standard orders or 13 days 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 the FKTN gene (OMIM 607440) cause muscular dystrophies in the dystroglycanopathy spectrum, the most severe of which is Walker-Warburg syndrome (WWS, OMIM 236670; Beltran-Valero de Bernabe et al. J Med Genet 40:845-848, 2003). Patients with WWS typically die at birth or shortly thereafter due to complications from severe CNS structural abnormalities. Fukuyama congenital muscular dystrophy (FCMD, OMIM 253800) is a less severe phenotype and is the second most common muscular dystrophy among Japanese people (Kobayashi et al. Nature 394:388-392, 1998). In the vast majority of cases the causative variant is an inserted 3 kb retrotransposon at the 3’ UTR of the FKTN gene. Patients who are compound heterozygous for the Japanese founder variant, and an FKTN coding variant may have more severe WWS-like features than homozygous founder variant patients (Kondo-Iida, et al. Hum Molec Genet 8:2303-2309, 1999). A third reported variant is limb girdle muscular dystrophy due to FKTN variants (LGMD2M, OMIM 611588; Godfrey et al. Ann Neurol 60:603-610, 2006). These patients are responsive to steroid treatment and, unlike WWS and FCMD patients, are able to ambulate and have normal intelligence and normal brain structure (Godfrey et al. Brain 130:2725-2735, 2007; Puckett et al. Neuromusc Disord 19:352-356, 2009). Although apparently rare, severe cardiomyopathy in the absence of significant skeletal muscle weakness or intellectual impairment has been reported in patients with FKTN variants (Murakami et al. Ann Neurol 60:597-602, 2006).

Genetics

The FKTN-related disorders are inherited in an autosomal recessive manner. Although the Japanese retrotransposon insertion variant is the most commonly reported pathogenic variant, variants of other forms are found throughout the gene (www.dmd.nl). Additional founder variants include the c.1167dupA variant in exon 9 in Ashkenazi Jewish individuals (Chang et al. Prenatal Diagnosis 29:560-569, 2009) and a deep intronic variant (c.647+2084G>T) that activates a pseudoexon within intron 5 among Koreans (Lim et al. Neuromuscul Disord 20:524-530, 2010). Variants in FKTN lead to reduced glycosylation of alphadystroglycan (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, FKRP, and LARGE) encode proteins required for processing of ADG, and that overlap exists between clinical phenotypes resulting from variants in these genes.

Clinical Sensitivity - Sequencing with CNV PG-Select

This test will not detect the Japanese founder variant underlying the Fukuyama congenital muscular dystrophy phenotype. If FCMD is suspected in a person of Japanese heritage, a separate test (#354) should be performed to rule-out presence of the ancestral variant. Because LGMD and CMD demonstrate extensive locus and allelic heterogeneity, a negative FKTN sequence result does not rule-out a diagnosis of these disorders 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 FKTN gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Additionally, this test includes the region of intron 5 including and surrounding the Korean c.647+2084G>T variant.

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 FKTN.

Gene

Official Gene Symbol OMIM ID
FKTN 607440
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Comprehensive Cardiology Panel
Fukuyama Congenital Muscular Dystrophy via the FKTN Japanese Founder Mutation
Sudden Cardiac Arrest Panel

Citations

  • Chang, W., et.al. (2009). PubMed ID: 19266496
  • de Bernabe, D. B., et.al. (2003). PubMed ID: 14627679
  • Ervasti, J. M., et.al. (1990). PubMed ID: 2188135
  • Godfrey C, Clement E, Mein R, Brockington M, Smith J, Talim B, Straub V, Robb S, Quinlivan R, Feng L, Jimenez-Mallebrera C, Mercuri E, et al. 2007. Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain 130: 2725–2735. PubMed ID: 17878207
  • Godfrey, C., et.al. (2006). PubMed ID: 17044012
  • Kobayashi, K., et.al. (1998). PubMed ID: 9690476
  • Kondo-Iida, E., et.al. (1999). PubMed ID: 10545611
  • Lim, B. C., et.al. (2010). PubMed ID: 20620061
  • Murakami, T., et.al. (2006). PubMed ID: 17036286
  • Puckett, R. L., et.al. (2009). PubMed ID: 19342235

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

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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.
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