Activated PI3K Delta Syndrome
Activated PI3K delta syndrome (APDS, also known as PASLI disease) is a primary immunodeficiency disease caused by activating gain of function mutations in the PIK3CD gene, which encodes the p110δ catalytic subunit of PI3Kδ. APDS-2 (PASLI-R1) is caused by exon-skipping mutations in PIK3R1 which encodes for the regulatory subunit p85α. APDS and APDS-2 patients present with similar symptoms, which include increased susceptibility to airway infections, bronchiectasis and lymphoproliferation.
Clinical trials
External links
- APDS Syndrome ()
- Genetics Home Reference entry: APDS ()
- Online Mendelian Inheritance in Man: APDS (OMIM #615513).
References
APDS
Jou ST, Chien YH, Yang YH, Wang TC, Shyur SD, Chou CC, Chang ML, Lin DT, Lin KH, Chiang BL. Identification of variations in the human phosphoinositide 3-kinase p110delta gene in children with primary B-cell immunodeficiency of unknown aetiology.
Angulo, I., O. Vadas, F. Garçon, E. Banham-Hall, V. Plagnol, T.R. Leahy, H. Baxendale, T. Coulter, J. Curtis, C. Wu, K. Blake-Palmer, O. Perisic, D. Smyth, M. Maes, C. Fiddler, J. Juss, D. Cilliers, G. Markelj, A. Chandra, G. Farmer, A. Kielkowska, J. Clark, S. Kracker, M. Debré, C. Picard, I. Pellier, N. Jabado, J.A. Morris, G. Barcenas-Morales, A. Fischer, L. Stephens, P. Hawkins, J.C. Barrett, M. Abinun, M. Clatworthy, A. Durandy, R. Doffinger, E. Chilvers, A.J. Cant, D. Kumararatne, K. Okkenhaug, R.L. Williams, A. Condliffe, and S. Nejentsev. Phosphoinositide 3-Kinase δ Gene Mutation Predisposes to Respiratory Infection and Airway Damage.
Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M, Stoddard J, Ouyang W, Frucht DM, Rao VK, Atkinson TP, Agharahimi A, Hussey AA, Folio LR, Olivier KN, Fleisher TA, Pittaluga S, Holland SM, Cohen JI, Oliveira JB, Tangye SG, Schwartzberg PL, Lenardo MJ, Uzel G. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency.
Kracker, S., J. Curtis, M. A. Ibrahim, A. Sediva, J. Salisbury, V. Campr, M. Debre, J. D. Edgar, K. Imai, C. Picard, J. L. Casanova, A. Fischer, S. Nejentsev, and A. Durandy. 2014. Occurrence of B-cell lymphomas in patients with activated phosphoinositide 3-kinase delta syndrome.
Crank, M. C., J. K. Grossman, S. Moir, S. Pittaluga, C. M. Buckner, L. Kardava, A. Agharahimi, H. Meuwissen, J. Stoddard, J. Niemela, H. Kuehn, and S. D. Rosenzweig. 2014. Mutations in PIK3CD Can Cause Hyper IgM Syndrome (HIGM) Associated with Increased Cancer Susceptibility.
Hartman, H. N., J. Niemela, M. K. Hintermeyer, M. Garofalo, J. Stoddard, J. W. Verbsky, S. D. Rosenzweig, and J. M. Routes. 2014. Gain of Function Mutations of PIK3CD as a Cause of Primary Sclerosing Cholangitis. J Clin Immunol.
Chiriaco, M., I. Brigida, P. Ariganello, S. Di Cesare, G. Di Matteo, F. Taus, D. Cittaro, D. Lazarevic, A. Scarselli, V. Santilli, E. Attardi, E. Stupka, S. Giannelli, M. Fraziano, A. Finocchi, P. Rossi, A. Aiuti, P. Palma, and C. Cancrini. 2015. A case of APDS patient: defects in maturation and function and decreased in vitro anti-mycobacterial activity in the myeloid compartment. Clin Immunol.
Elgizouli, M., D. M. Lowe, C. Speckmann, D. Schubert, J. Hulsdunker, Z. Eskandarian, A. Dudek, A. Schmitt-Graeff, J. Wanders, S. F. Jorgensen, B. Fevang, U. Salzer, A. Nieters, S. Burns, and B. Grimbacher. 2016. Activating PI3Kdelta mutations in a cohort of 669 patients with primary immunodeficiency. Clin Exp Immunol 183:221-229.
APDS-2
Deau, M. C., L. Heurtier, P. Frange, F. Suarez, C. Bole-Feysot, P. Nitschke, M. Cavazzana, C. Picard, A. Durandy, A. Fischer, and S. Kracker. 2014. A human immunodeficiency caused by mutations in the PIK3R1 gene. J Clin Invest 124:3923-3928.
Lucas, C. L., Y. Zhang, A. Venida, Y. Wang, J. Hughes, J. McElwee, M. Butrick, H. Matthews, S. Price, M. Biancalana, X. Wang, M. Richards, T. Pozos, I. Barlan, A. Ozen, V. K. Rao, H. C. Su, and M. J. Lenardo. 2014. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. J Exp Med 211:2537-2547.
Lougaris, V., F. Faletra, G. Lanzi, D. Vozzi, A. Marcuzzi, E. Valencic, E. Piscianz, A. Bianco, M. Girardelli, M. Baronio, C. Loganes, A. Fasth, F. Salvini, A. Trizzino, D. Moratto, F. Facchetti, S. Giliani, A. Plebani, and A. Tommasini. 2015. Altered germinal center reaction and abnormal B cell peripheral maturation in PI3KR1-mutated patients presenting with HIGM-like phenotype. Clin Immunol 159:33-36.
Kuhlen, M., A. Hönscheid, L. Loizou, S. Nabhani, U. Fischer, P. Stepensky, J. Schaper, W. Klapper, M. Siepermann, F. Schuster, R. Meisel, and A. Borkhardt. 2016. De novo PIK3R1 gain-of-function with recurrent sinopulmonary infections, long-lasting chronic CMV-lymphadenitis and microcephaly. Clinical Immunology 162:27-30.