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Novel IL2RG Mutation Causes Leaky TLOWB+NK+ SCID With Nodular Regenerative Hyperplasia and Normal IL-15 STAT5 Phosphorylation

Neves, João F., MD*,†; Martins, Catarina, PhD; Cordeiro, Ana I., MD*; Neves, Conceição, MD*; Plagnol, Vicent, PhD; Curtis, James, BSc§; Fabre, Monique, MD; Bibi, Shahnaz, MSc; Borrego, Luis M., PhD†,#; Moshous, Despina, PhD**; Nejentsev, Sergey, PhD§; Gilmour, Kimberly, PhD††

Journal of Pediatric Hematology/Oncology: May 2019 - Volume 41 - Issue 4 - p 328–333
doi: 10.1097/MPH.0000000000001232
Clinical and Laboratory Observations

X-linked severe combined immunodeficiency disease (SCID) is caused by mutations in the interleukin (IL)-2 receptor γ (IL2RG) gene and patients usually present with a TB+NK SCID phenotype. Nevertheless, a minority of these patients present with a TB+NK+ phenotype, similar to the IL-7R-deficient patients. We report a patient with a novel missense p.Glu297Gly mutation in the IL2RG gene presenting with a leaky TlowB+NK+ SCID with delayed onset, moderate susceptibility to infections, and nodular regenerative hyperplasia. He presents with preserved STAT5 tyrosine phosphorylation in response to IL-15 stimulation but not in response to IL-2 and IL-7, resulting in the NK+ phenotype.

*Primary Immunodeficiencies Unit; Hospital Dona Estefânia—CHLC, EPE

#Immunoallergy Department, Hospital CUF Descobertas, Lisbon

CEDOC, Chronic Diseases Research Center, NOVA Medical School, Lisboa, Portugal

University College London Genetics Institute, University College London

Regional Molecular Genetics Laboratory

††Department of Immunology, Great Ormond Street Hospital, London

§Department of Medicine, University of Cambridge, Cambridge, UK

Pathology Department

**Immunology, Hematology, Rheumatology Unit, Necker Enfants Malades Hospital, HPHP, Paris, France

K.G. was funded by the NIHR Great Ormond Street Hospital Biomedical Research Centre. S.N. is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.

The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

J.F.N.: designed the research study and wrote the paper. C.M. and L.M.B.: performed immunologic analysis. A.I.C. and C.N.: medical doctor of the patient and designed the research study. M.F.: performed histopathologic analysis and illustrations. V.P., J.C., S.B., and S.N.: performed genetical analysis. D.M.: performed HSCT and analyzed the data. K.G.: performed the research and analyzed the data.

The authors declare no conflict of interest.

Reprints: João F. Neves, MD, Infectious Diseases Unit; Primary Immunodeficiencies Unit, Hospital Dona Estefania, Pediatric University Hospital Rua Jacinta Marto, Lisbon 1169-045, Portugal (e-mails:;

Received December 6, 2017

Accepted April 17, 2018

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