Case Report: A Novel IL2RG Frame-Restoring Rescue Mutation Mimics Early T Cell Engraftment Following Haploidentical Hematopoietic Stem Cell Transplantation in a Patient With X-SCID.
IL2RG
X-SCID
early engraftment
hematopoietic stem cell transplantation
second-site mutation
severe combined immunodeficiency
somatic mosaicism
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
21
12
2020
accepted:
23
03
2021
entrez:
7
5
2021
pubmed:
8
5
2021
medline:
24
9
2021
Statut:
epublish
Résumé
Mutations of the interleukin 2 receptor γ chain (IL2RG) result in the most common form of severe combined immunodeficiency (SCID), which is characterized by severe and persistent infections starting in early life with an absence of T cells and natural killer cells, normal or elevated B cell counts and hypogammaglobulinemia. SCID is commonly fatal within the first year of life, unless the immune system is reconstituted by hematopoietic stem cell transplantation (HSCT) or gene therapy. We herein describe a male infant with X-linked severe combined immunodeficiency (X-SCID) diagnosed at 5 months of age. Genetic testing revealed a novel C to G missense mutation in exon 1 resulting in a 3' splice site disruption with premature stop codon and aberrant IL2 receptor signaling. Following the diagnosis of X-SCID, the patient subsequently underwent a TCRαβ/CD19-depleted haploidentical HSCT. Post transplantation the patient presented with early CD8
Identifiants
pubmed: 33959125
doi: 10.3389/fimmu.2021.644687
pmc: PMC8093767
doi:
Substances chimiques
IL2RG protein, human
0
Interleukin Receptor Common gamma Subunit
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
644687Informations de copyright
Copyright © 2021 Steininger, Leiss-Piller, Geier, Rossmanith, Elfeky, Bra, Pichler, Lawitschka, Zubarovskaya, Artacker, Matthes-Leodolter, Eibl and Wolf.
Déclaration de conflit d'intérêts
Author ME was employed by company Biomedizinische Forschungs GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Cell. 1993 Apr 9;73(1):147-57
pubmed: 8462096
Curr Opin Allergy Clin Immunol. 2008 Dec;8(6):510-4
pubmed: 18978464
J Pediatr. 1993 Oct;123(4):564-72
pubmed: 8410508
N Engl J Med. 1999 Feb 18;340(7):508-16
pubmed: 10021471
Blood. 2002 Feb 1;99(3):1005-13
pubmed: 11807006
JAMA. 2014 Aug 20;312(7):729-38
pubmed: 25138334
J Allergy Clin Immunol. 2017 Feb;139(2):628-633.e10
pubmed: 27444177
Lancet Haematol. 2015 May;2(5):e194-203
pubmed: 26688094
J Allergy Clin Immunol. 2017 Dec;140(6):1643-1650.e9
pubmed: 28392330
Immunol Res. 2019 Jun;67(2-3):166-175
pubmed: 31222511
J Pediatr. 1997 Mar;130(3):378-87
pubmed: 9063412
Lancet. 2003 Feb 15;361(9357):553-60
pubmed: 12598139
Blood. 2001 Sep 15;98(6):1847-51
pubmed: 11535520
Am J Hum Genet. 1994 Jul;55(1):59-68
pubmed: 8023852
J Allergy Clin Immunol. 2010 Sep;126(3):602-10.e1-11
pubmed: 20673987
Blood. 2018 Oct 25;132(17):1737-1749
pubmed: 30154114
J Allergy Clin Immunol. 2003 Nov;112(5):973-80
pubmed: 14610491
J Clin Invest. 1995 Mar;95(3):1169-73
pubmed: 7883965
Front Pediatr. 2019 Sep 24;7:381
pubmed: 31616648
Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9466-70
pubmed: 7937790
Blood. 2008 Sep 1;112(5):1872-5
pubmed: 18559672
Blood. 2008 Nov 15;112(10):4090-7
pubmed: 18728247
Blood. 2001 May 1;97(9):2896-9
pubmed: 11313286
J Clin Immunol. 2015 Oct;35(7):610-4
pubmed: 26407811
Front Pediatr. 2019 Aug 08;7:295
pubmed: 31440487
Blood. 2005 Sep 15;106(6):2099-101
pubmed: 15845893
Biol Blood Marrow Transplant. 2017 Mar;23(3):491-497
pubmed: 27888015
Nat Rev Dis Primers. 2015 Oct 29;1:15061
pubmed: 27189259
N Engl J Med. 1996 Nov 21;335(21):1563-7
pubmed: 8900089
Blood. 2001 Mar 1;97(5):1491-7
pubmed: 11222398
J Allergy Clin Immunol. 2019 Jul;144(1):280-293
pubmed: 30731121
N Engl J Med. 2014 Jul 31;371(5):434-46
pubmed: 25075835
Adv Exp Med Biol. 2019;1172:1-19
pubmed: 31628649
Int J Hematol. 2002 Nov;76(4):295-8
pubmed: 12463590
Expert Rev Clin Immunol. 2019 Jul;15(7):735-751
pubmed: 31070946
Immunol Rev. 2005 Feb;203:98-109
pubmed: 15661024
Lancet. 1968 Dec 28;2(7583):1366-9
pubmed: 4177932
Blood. 2018 Jun 28;131(26):2967-2977
pubmed: 29728406
Blood. 2016 Jan 28;127(4):503-12
pubmed: 26644451
Blood. 2017 Aug 3;130(5):677-685
pubmed: 28588018
Front Immunol. 2018 Jul 26;9:1672
pubmed: 30093901
Immunogenetics. 2017 Jan;69(1):29-38
pubmed: 27566612
Scand J Immunol. 2011 Nov;74(5):471-81
pubmed: 21671975
Nat Genet. 1996 Jul;13(3):290-5
pubmed: 8673127
J Immunol. 2001 Apr 15;166(8):5245-9
pubmed: 11290809
Annu Rev Immunol. 2004;22:625-55
pubmed: 15032591
J Allergy Clin Immunol. 2018 Apr;141(4):1417-1426.e1
pubmed: 28780238
Blood. 2014 Jul 31;124(5):822-6
pubmed: 24869942
J Clin Immunol. 2014 Nov;34(8):941-53
pubmed: 25205547
Clin Lab Haematol. 2000 Apr;22(2):81-7
pubmed: 10792397
Biol Blood Marrow Transplant. 2013 Nov;19(11):1581-9
pubmed: 23939199
Blood. 2004 Jun 15;103(12):4565-72
pubmed: 14726382
J Clin Immunol. 2018 Jan;38(1):96-128
pubmed: 29226302
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):274-8
pubmed: 10618408
Front Immunol. 2014 Apr 22;5:162
pubmed: 24795713
Immunol Rev. 2004 Dec;202:67-83
pubmed: 15546386
Genes Dis. 2019 Jul 30;7(1):38-51
pubmed: 32181274
Br J Haematol. 2012 Mar;156(5):656-66
pubmed: 22224700
J Clin Immunol. 2019 Jul;39(5):505-511
pubmed: 31172381
Blood. 1996 Sep 1;88(5):1708-17
pubmed: 8781427