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IRF6-Related Disorders via the IRF6 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
IRF6 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8621IRF681479 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

  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

IRF6-related disorders span a spectrum from isolated cleft lip and palate and Van der Woude syndrome (VWS; OMIM#119300) at the mild end to popliteal pterygium syndrome (PPS; OMIM 119500) at the more severe end. Anomalies found in individuals with VWS include congenital, usually bilateral, paramedian lower-lip fistulae (pits), cleft lip (CL), and cleft palate (CP). The PPS phenotype includes CL/CP, fistulae of the lower lip, webbing of the skin extending from the ischial tuberosities to the heels, bifid scrotum and cryptorchidism in males, hypoplasia of the labia majora in females, syndactyly of fingers or toes, and anomalies of the skin around the nails. Filiform synechiae may connect the upper and lower jaws (syngnathia) or the upper and lower eyelids (ankyloblepharon). A characteristic pyramidal fold of skin overlying the nail of the hallux is almost pathognomonic (Durda et al. GeneReviews 2011). In both VWS and PPS, growth and intelligence are normal.

Genetics

Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) are inherited in an autosomal dominant manner. Most individuals with these two conditions have an affected parent; however, penetrance is incomplete and de novo variants have been reported. IRF6 is the only gene currently known to be associated with VWS and PPS. IRF6 encodes interferon regulatory factor 6, the function of which is currently unknown. However, IRF6 protein belongs to the interferon regulatory factor family of transcription factors. The IRFs are best known to regulate the expression of interferon-alpha and interferon-beta after viral infection (Taniguchi et al. Annu Rev Immunol 19:623-655, 2001). This protein family shares a highly-conserved helix-loop-helix DNA binding domain and a less well-conserved protein binding domain. Missense, nonsense, and frameshift variants as well as gross deletions in IRF6 have been reported to cause disease. The variants in individuals with VWS are consistent with haploinsufficiency. Those missense variants causing VWS are localized to the regions encoding the DNA binding domains (exons 3-4) and the protein binding domain (exons 7-9) and most likely result in loss of function. The variants in many individuals with PPS are localized to the DNA binding domain, which are predicted to abrogate DNA binding and likely have a dominant-negative effect on the protein function (Escalante et al. Nature 391:103–106, 1998; Kondo et al. Nat Genet 32:285–289, 2002; de Lima et al. Genet Med 11:241–247, 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect disease variants in about 70% of individuals with the VWS and 97% of individuals with the PPS (Durda et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the IRF6 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

Candidates for this test are patients with clinical features consistent with VWS or PPS and family members of patients with known IRF6 variants.

Gene

Official Gene Symbol OMIM ID
IRF6 607199
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • de Lima et al. Genet Med 11:241–247, 2009 PubMed ID: 19282774
  • Durda et al. Gene Reviews 2011 PubMed ID: 20301581
  • Escalante et al. Nature 391:103–106, 1998 PubMed ID: 942251
  • Kondo et al. Nat Genet 32:285–289 PubMed ID: 12219090
  • Taniguchi et al. Annu Rev Immunol 19:623-655, 2001 PubMed ID: 11244049

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)


1) Select Test Type


2) Select Additional Test Options

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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