Abstract
Background and Objective: APDS [Activated phosphoinositide 3-kinase (PI3K) δ Syndrome]
is a newly found special form of primary immunodeficiency caused by mutations in genes
encoding PI3Kδ subunits and over-activation of the PI3K signaling pathway. Gain-of-function and
loss-of-function mutations in PIK3CD (encoding P110δ) and PIK3R1 (encoding p85α, p55α and p50α)
lead to APDS1 and APDS2, respectively. The subsequent irregular PI3K downstream signaling cascade
is associated with abnormalities in B cells and T cells and the consequent heterogeneous clinical
manifestations including respiratory tract infections, autoimmunity, lymphoproliferation and not to
mention primary antibody deficiency. In this study, we report a 12-year-old girl with a mutation in the
PIK3R1 gene who manifested immunological phenotypes resembling hyper IgM syndrome along with
a review of the literature of the previously reported patients.
Methods: Whole exome sequencing was performed to detect the underlying genetic mutation in this
patient.
Results: A de novo heterozygous splice site mutation in the hot spot of the PIK3R1 gene within the
intron 10 was found (c.1425+1G>A).
Conclusion: Further investigations are required for evaluation of the underlying genetic defects and
the possible associations between genetic underpinning and heterogeneous severity and features of the
disease.
Keywords:
Primary immunodeficiency, Activated phosphoinositide 3-kinase Delta Syndrome (APDS), APDS2, PASLI-R1,
Hyper IgM syndrome, PIK3R1, p85α.
Graphical Abstract
[10]
Maccari, M.E.; Abolhassani, H.; Aghamohammadi, A.; Aiuti, A.; Aleinikova, O.; Bangs, C.; Baris, S.; Barzaghi, F.; Baxendale, H.; Buckland, M.; Burns, S.O.; Cancrini, C.; Cant, A.; Cathébras, P.; Cavazzana, M.; Chandra, A.; Conti, F.; Coulter, T.; Devlin, L.A.; Edgar, J.D.M.; Faust, S.; Fischer, A.; Garcia-Prat, M.; Hammarström, L.; Heeg, M.; Jolles, S.; Karakoc-Aydiner, E.; Kindle, G.; Kiykim, A.; Kumararatne, D.; Grimbacher, B.; Longhurst, H.; Mahlaoui, N.; Milota, T.; Moreira, F.; Moshous, D.; Mukhina, A.; Neth, O.; Neven, B.; Nieters, A.; Olbrich, P.; Ozen, A.; Pachlopnik Schmid, J.; Picard, C.; Prader, S.; Rae, W.; Reichenbach, J.; Rusch, S.; Savic, S.; Scarselli, A.; Scheible, R.; Sediva, A.; Sharapova, S.O.; Shcherbina, A.; Slatter, M.; Soler-Palacin, P.; Stanislas, A.; Suarez, F.; Tucci, F.; Uhlmann, A.; van Montfrans, J.; Warnatz, K.; Williams, A.P.; Wood, P.; Kracker, S.; Condliffe, A.M.; Ehl, S. Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry.
Front. Immunol., 2018,
9, 543.
[
http://dx.doi.org/10.3389/fimmu.2018.00543] [PMID:
29599784]
[11]
Elkaim, E.; Neven, B.; Bruneau, J.; Mitsui-Sekinaka, K.; Stanislas, A.; Heurtier, L.; Lucas, C.L.; Matthews, H.; Deau, M.C.; Sharapova, S.; Curtis, J.; Reichenbach, J.; Glastre, C.; Parry, D.A.; Arumugakani, G.; McDermott, E.; Kilic, S.S.; Yamashita, M.; Moshous, D.; Lamrini, H.; Otremba, B.; Gennery, A.; Coulter, T.; Quinti, I.; Stephan, J.L.; Lougaris, V.; Brodszki, N.; Barlogis, V.; Asano, T.; Galicier, L.; Boutboul, D.; Nonoyama, S.; Cant, A.; Imai, K.; Picard, C.; Nejentsev, S.; Molina, T.J.; Lenardo, M.; Savic, S.; Cavazzana, M.; Fischer, A.; Durandy, A.; Kracker, S. Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study.
J. Allergy Clin. Immunol., 2016,
138(1), 210-218.e9.
[
http://dx.doi.org/10.1016/j.jaci.2016.03.022] [PMID:
27221134]
[16]
Aghamohammadi, A.; Mohammadinejad, P.; Abolhassani, H.; Mirminachi, B.; Movahedi, M.; Gharagozlou, M.; Parvaneh, N.; Zeiaee, V.; Mirsaeed-Ghazi, B.; Chavoushzadeh, Z.; Mahdaviani, A.; Mansouri, M.; Yousefzadegan, S.; Sharifi, B.; Zandieh, F.; Hedayat, E.; Nadjafi, A.; Sherkat, R.; Shakerian, B.; Sadeghi-Shabestari, M.; Hosseini, R.F.; Jabbari-Azad, F.; Ahanchian, H.; Behmanesh, F.; Zandkarimi, M.; Shirkani, A.; Cheraghi, T.; Fayezi, A.; Mohammadzadeh, I.; Amin, R.; Aleyasin, S.; Moghtaderi, M.; Ghaffari, J.; Arshi, S.; Javahertrash, N.; Nabavi, M.; Bemanian, M.H.; Shafiei, A.; Kalantari, N.; Ahmadiafshar, A.; Khazaei, H.A.; Atarod, L.; Rezaei, N. Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry.
J. Clin. Immunol., 2014,
34(4), 478-490.
[
http://dx.doi.org/10.1007/s10875-014-0001-z] [PMID:
24659230]
[22]
Bravo, G-M.M.; Garcia-Minaur, S. Molina, Garicano, J.; Santos, Simarro, F.; Del, Pino, Molina, L.; Lopez-Granados, E.; Ferreira, Cerdan, A.; Rodriguez, Pena, R. Mutations in PIK3R1 can lead to APDS2, SHORT syndrome or a combination of the two. Clin. Immunol., 2017, 179, 77-80.
Download PDF Flyer