Atypical immune phenotype in severe combined immunodeficiency patients with novel mutations in IL2RG and JAK3

Lior Goldberg, Amos J. Simon, Atar Lev, Ortal Barel, Tali Stauber, Vered Kunik, Gideon Rechavi, Raz Somech

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Mutations in the common gamma chain of the interleukin 2 receptor (IL2RG) or the associated downstream signaling enzyme Janus kinase 3 (JAK3) genes are typically characterized by a T cell-negative, B cell-positive, natural killer (NK) cell-negative (TB+NK) severe combined immunodeficiency (SCID) immune phenotype. We report clinical course, immunological, genetic and proteomic work-up of two patients with different novel mutations in the IL-2-JAK3 pathway with a rare atypical presentation of TB+NK SCID. Lymphocyte subpopulation revealed significant T cells lymphopenia, normal B cells, and NK cells counts (T−B+NK+SCID). Despite the presence of B cells, IgG levels were low and IgA and IgM levels were undetectable. T-cell proliferation in response to mitogens in patient 1 was very low and T-cell receptor V-beta chain repertoire in patient 2 was polyclonal. Whole-exome sequencing revealed novel mutations in both patients (patient 1—c.923delC frame-shift mutation in the IL2RG gene, patient 2—c.G172A a homozygous missense mutation in the JAK3 gene). Bioinformatic analysis of the JAK3 mutation indicated deleterious effect and 3D protein modeling located the mutation to a surface exposed alpha-helix structure. Our findings help to link between genotype and phenotype, which is a key factor for the diagnosis and treatment of SCID patients.

Original languageEnglish
Pages (from-to)326-334
Number of pages9
JournalGenes and Immunity
Issue number5
StatePublished - Nov 2020
Externally publishedYes

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© 2020, The Author(s), under exclusive licence to Springer Nature Limited.


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