Dystroglycanopathy via the FKTN Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
343 FKTN$610.00 81405 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

This test will not detect the Japanese founder mutation 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 mutation. 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.

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 FKTN$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Features

Mutations 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 mutation is an inserted 3 kb retrotransposon at the 3’ UTR of the FKTN gene. Patients who are compound heterozygous for the Japanese founder mutation and an FKTN coding mutation may have more severe WWS-like features than homozygous founder mutation patients (Kondo-Iida, et al. Hum Molec Genet 8:2303-2309, 1999). A third reported variant is limb girdle muscular dystrophy due to FKTN mutations (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 mutations (Murakami et al. Ann Neurol 60:597-602, 2006).


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

Testing Strategy

Fukutin is coded by exons 2-10 of the FKTN gene located on chromosome 9q31. Testing is accomplished by amplifying the coding exons and ~10 bp of adjacent noncoding sequence plus the region of intron 5 including and surrounding the Korean c.647+2084G>T mutation, then determining the nucleotide sequence using standard dideoxy sequencing methods and a capillary electrophoresis instrument. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.

Indications for Test

Individuals with symptoms consistent with LGMD or CMD. Individuals with immunofluorescence results demonstrating hypoglycosylation of ADG in muscle.


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


Genetic Counselors
  • Chang, W., (2009). PubMed ID: 19266496
  • de Bernabe, D. B., (2003). PubMed ID: 14627679
  • Ervasti, J. M., (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., (2006). PubMed ID: 17044012
  • Kobayashi, K., (1998). PubMed ID: 9690476
  • Kondo-Iida, E., (1999). PubMed ID: 10545611
  • Lim, B. C., (2010). PubMed ID: 20620061
  • Murakami, T., (2006). PubMed ID: 17036286
  • Puckett, R. L., (2009). PubMed ID: 19342235
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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