Disease

Activated PI3K-Delta Immunodeficiency Syndrome

Description

The PIK3CD gene encodes the p110δ subunit of phosphoinositide 3-kinase (PI3K) and is expressed in immune cells, specifically leukocytes. Mutations in this gene have been reported to cause T-cell defects, thus the implication of immune deficiency phenotype in affected individuals.

Activated PI3K-delta immunodeficiency syndrome (APDS) is a primary immunodeficiency characterized by recurrent sinopulmonary infections, EBV- and CMV-associated viremia, abnormal B- and T-cell functions and hemolytic anemia.  Many patients develop lymphadenopathy, mucoid lymphoid aggregates and have an increased susceptibility to B cell lymphoma.

Indications

Confirmation of diagnosis in a patient with the following:

  • Activated PI3K-delta syndrome (APDS)/ Immunodeficiency 14
  • Primary B cell immunodeficiency
  • Family members with previously identified PIK3CD mutation

Testing Methodology

Testing is performed by Sanger sequencing of the entire coding regions and intron/exon boundaries of the PIK3CD gene. 

Test Sensitivity

Clinical Sensitivity

Lucas et al. (2014) identified 3 different heterozygous gain-of-function mutations in the PIK3CD gene in 14 patients from 7 unrelated families with IMD14/APDS. 

Analytical Sensitivity

The sensitivity of DNA sequencing is over 99% for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed.

Mutations in regulatory regions or other untranslated regions are not detected by this test. Large deletions involving entire single exons or multiple exons, large insertions and other complex genetic events have been reported in many of these genes and will not be identified using this test methodology. Rare primer site variants may lead to erroneous results.  

Turnaround Time

28 days

References

Angulo, I., O. Vadas, et al. (2013) "Phosphoinositide 3-Kinase Delta Gene Mutation Predisposes to Respiratory Infection and Airway Damage." Science 342(6160): 866–71.

Jou, S.T., Y.H. Chien, et al. (2006) "Identification of Variations in the Human Phosphoinositide 3-Kinase p110delta Gene in Children with Primary B-Cell Immunodeficiency of Unknown Aetiology." Int J Immunogenet 33(5): 361–9.

Lucas, C.L., H.S. Kuehn, et al. (2014) "Dominant-Activating Germline Mutations in the Gene Encoding the PI(3)K Catalytic Subunit p110delta Result in T Cell Senescence and Human Immunodeficiency." Nat Immunol 15(1): 88–97.