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Primary Immunodeficiency via the PIK3CD 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
9849 PIK3CD 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9849PIK3CD81479 81479,81479 $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.

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

  • Megan Piazza, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Primary immunodeficiency (PID) via the PIK3CD gene is a disorder hallmarked by recurrent sinopulmonary infections, impaired vaccine response, and chronic viremia due to Epstein-Barr virus (EBV) and/or cytomegalovirus. Recurrent respiratory infections can lead to progressive airway damage resulting in bronchiectasis (Angulo et al. 2013; Lucas et al. 2014). Because of an impaired immune response to EBV, patients with PID via the PIK3CD gene are at increased risk for development of EBV-related lymphoma (Crank et al. 2014). To date, over 50 genes have been implicated in PID, with mutations in the PIK3CD gene first being described in late 2013 (Al-Herz et al. 2014). Genetic testing is helpful in the differential diagnosis of PID via PIK3CD from other PIDs including hyper-IgM syndrome, agammaglobulinemia, and common variable immunodeficiency. Treatment for disease may include immunoglobulin replacement and antibiotics during infection bouts. Allogenic stem cell transplantation is the only curative treatment (Angulo et al. 2013).

Genetics

PID via mutations in the PIK3CD gene is inherited in an autosomal dominant manner. Both familial and spontaneous forms of the disease have been documented. To date, gain of function mutations leading to hyperactivation of PIK3CD are the cause of PID with c.3061G>A (p. Glu1021Lys) and c.1573G>A (p.Glu525Lys) variants being most prevalent (Angulo et al. 2013; Lucas et al. 2014). There are no reports of nonsense, frameshift, insertion, or deletion mutations in the PIK3CD gene to date. Somatic mutations in the PIK3CD have also been found in patients with Diffuse Large B-cell lymphoma (Zhang et al. 2013; Kang et al. 2006). The PIK3CD gene encodes the p100 subunit of phosphatidylinositol-3-OH kinase which is expressed only in leukocytes (Chantry et al. 1997; VanHaesebroeck et al. 1997). The PIK3CD protein is an important second messenger kinase involved in several functions including migration, survival, and immunoglobulin class switching (Foukas et al. 2006; Ali et al. 2004).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of patients have been reported. Analytical sensitivity should be high because all mutations reported are detectable by this method.

Testing Strategy

This test provides full coverage of all coding exons of the PIK3CD 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 testing have recurrent respiratory infections and lymphoproliferation of CD3+ T-cell and CD20+ B-cell populations. Patients also tend to have decreased CD4+ helper T-cell and impaired immunoglobin class switching leading to decrease IgA levels (Lucas et al. 2013; Angulo et al. 2013).

Gene

Official Gene Symbol OMIM ID
PIK3CD 602839
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Immunodeficiency 14 AD 615513

Related Tests

Name
Autoimmune Lymphoproliferative Syndrome/ALPS Panel
Common Variable Immune Deficiency/IgA Deficiency via the TNFRSF13B Gene
Hyper IgM Syndrome Panel
X-linked Agammaglobulinemia via the BTK Gene
X-Linked Hyper IgM Syndrome via the CD40LG Gene

Citations

  • Al-Herz W, Bousfiha A, Casanova J-L, Chatila T, Conley ME, Cunningham-Rundles C, Etzioni A, Franco JL, Gaspar HB, Holland SM, Klein C, Nonoyama S, et al. 2014. Corrigendum: Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Frontiers in Immunology 5: PubMed ID: 25309542
  • Ali K, Bilancio A, Thomas M, Pearce W, Gilfillan AM, Tkaczyk C, Kuehn N, Gray A, Giddings J, Peskett E, Fox R, Bruce I, et al. 2004. Essential role for the p110delta phosphoinositide 3-kinase in the allergic response. Nature 431: 1007–1011. PubMed ID: 15496927
  • Angulo I, Vadas O, Garcon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, Blake-Palmer K, Perisic O, et al. 2013. Phosphoinositide 3-Kinase Gene Mutation Predisposes to Respiratory Infection and Airway Damage. Science 342: 866–871. PubMed ID: 24136356
  • Chantry D, Vojtek A, Kashishian A, Holtzman DA, Wood C, Gray PW, Cooper JA, Hoekstra MF. 1997. p110 , a Novel Phosphatidylinositol 3-Kinase Catalytic Subunit That Associates with p85 and Is Expressed Predominantly in Leukocytes. Journal of Biological Chemistry 272: 19236–19241. PubMed ID: 9235916
  • Crank MC, Grossman JK, Moir S, Pittaluga S, Buckner CM, Kardava L, Agharahimi A, Meuwissen H, Stoddard J, Niemela J, Kuehn H, Rosenzweig SD. 2014. Mutations in PIK3CD Can Cause Hyper IgM Syndrome (HIGM) Associated with Increased Cancer Susceptibility. Journal of Clinical Immunology 34: 272–276. PubMed ID: 24610295
  • Foukas LC, Claret M, Pearce W, Okkenhaug K, Meek S, Peskett E, Sancho S, Smith AJH, Withers DJ, Vanhaesebroeck B. 2006. Critical role for the p110α phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature 441: 366–370. PubMed ID: 16625210
  • Kang S, Denley A, Vanhaesebroeck B, Vogt PK. 2006. Oncogenic transformation induced by the p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase. Proc. Natl. Acad. Sci. U.S.A. 103: 1289–1294. PubMed ID: 16432180
  • Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M, Stoddard J, Ouyang W, et al. 2013. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency. Nature Immunology 15: 88–97. PubMed ID: 24165795
  • Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD. 1997. p110δ, a novel phosphoinositide 3-kinase in leukocytes. Proceedings of the National Academy of Sciences 94: 4330–4335. PubMed ID: 9113989
  • Zhang J, Grubor V, Love CL, Banerjee A, Richards KL, Mieczkowski PA, Dunphy C, Choi W, Au WY, Srivastava G, Lugar PL, Rizzieri DA, et al. 2013. Genetic heterogeneity of diffuse large B-cell lymphoma. Proceedings of the National Academy of Sciences 110: 1398–1403. PubMed ID: 23292937

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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