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Popliteal Pterygium Syndrome 2, Lethal Type via the RIPK4 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
8353 RIPK4 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8353RIPK481479 81479(x2) $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. 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 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

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

  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Popliteal pterygium syndrome 2, lethal type (also called Bartsocas-Papas syndrome, or multiple pterygium syndrome, ASLAN type) is featured by multiple popliteal pterygia, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and syndactyly. Other clinical features may include clubfeet, nail hypoplasia, genital anomalies, flexion contractures and arthrogryposis of joints, cutis aplasia, widely spaced nipples, low-set umbilicus, and unilateral renal hypoplasia. Early death is common; however, some patients have survived into childhood (Mitchell et al. 2012). In addition to popliteal pterygium syndrome, defects in RIPK4 also cause autism spectrum disorder (Bi et al. 2012). A homozygous RIPK4 mutation was also identified in a patient affected with Hay-Wells like syndrome presenting with ankyloblepharon-ectodermal defects-cleft lip/palate (Gripp et al. 2013).

Genetics

Popliteal pterygium syndrome 2, lethal type is an autosomal recessive disorder caused by mutations in the RIPK4 gene. The RIPK4 protein (Receptor-interacting protein kinase, also called RIP4) coded by the RIPK4 gene belongs to a RIP kinase family of serine/threonine protein kinases that regulate NF-kb and JNK function. RIPK4 contains an N-terminal RIP-like kinase motif, a Ser/Thr- rich domain, and a C-terminal 11 ankyrin repeats. Studies suggested that RIPK4 serves as a target of TP63 and is required for epidermal development (Meylan et al. 2002). To date, only 7 unique pathogenic mutations have been identified. They are: 5 missense, 1 nonsense and 1 small duplication (Human Gene Mutation Database; Kalay et al. 2012; Mitchell et al. 2012, Bi et al. 2012 and Gripp et al. 2013). No large deletions and duplications have been reported.

Clinical Sensitivity - Sequencing with CNV PGxome

Due to limited publications, clinical sensitivity is currently unknown. The mutation detection rate by sequencing should be high, because only seven unique RIPK4 pathogenic variants have been reported. They all are point mutations and can be detected by sequencing (Human Gene Mutation Database; Kalay et al. 2012; Mitchell et al. 2012, Bi et al. 2012 and Gripp et al. 2013).

No large deletions or duplications have been reported to date in the RIPK4 gene (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the RIPK4 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 symptoms consistent with autosomal recessive popliteal pterygium syndrome and the family members of patients who have known RIPK4 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RIPK4.

Gene

Official Gene Symbol OMIM ID
RIPK4 605706
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Popliteal pterygium syndrome 2, lethal type AR 263650

Related Test

Name
TP63-Related Disorders via the TP63 Gene

Citations

  • Bi C, Wu J, Jiang T, Liu Q, Cai W, Yu P, Cai T, Zhao M, Jiang Y, Sun ZS. 2012. Mutations of ANK3 identified by exome sequencing are associated with autism susceptibility. Hum. Mutat. 33: 1635–1638. PubMed ID: 22865819
  • Gripp KW, Ennis S, Napoli J. 2013. Exome analysis in clinical practice: expanding the phenotype of Bartsocas-Papas syndrome. Am. J. Med. Genet. A 161A: 1058–1063. PubMed ID: 23610050
  • Human Gene Mutation Database (Bio-base).
  • Kalay E, Sezgin O, Chellappa V, Mutlu M, Morsy H, Kayserili H, Kreiger E, Cansu A, Toraman B, Abdalla EM, Aslan Y, Pillai S, et al. 2012. Mutations in RIPK4 Cause the Autosomal-Recessive Form of Popliteal Pterygium Syndrome. The American Journal of Human Genetics 90: 76–85. PubMed ID: 22197489
  • Meylan E, Martinon F, Thome M, Gschwendt M, Tschopp J. 2002. RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF-?B and is processed during apoptosis. EMBO Rep 3: 1201–1208. PubMed ID: 12446564
  • Mitchell K, O’Sullivan J, Missero C, Blair E, Richardson R, Anderson B, Antonini D, Murray JC, Shanske AL, Schutte BC, Romano R-A, Sinha S, et al. 2012. Exome Sequence Identifies RIPK4 as the Bartsocas- Papas Syndrome Locus. Am J Hum Genet 90: 69–75. PubMed ID: 22197488

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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