Activated PI3K-Delta Immunodeficiency
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.
Confirmation of diagnosis in a patient with the following:
- Activated PI3K-delta syndrome (APDS)/
- Primary B cell immunodeficiency
- Family members with previously identified
Testing is performed by Sanger sequencing of the entire coding regions and intron/exon boundaries of the PIK3CD gene.
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.
The sensitivity of DNA sequencing is over 99% for the
detection of nucleotide base changes, small deletions and insertions in the
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.
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.