A novel IL2RG mutation associated with maternal T lymphocyte engraftment in a patient with severe combined immunodeficiency

Abstract

Severe combined immunodeficiency (SCID) represents a genetically heterogeneous group of primary immunodeficiency disorders. Irrespective of the genetic defect, patients with SCID may be engrafted with transplacentally derived maternal T-lymphocytes that in a subset of cases may be responsive to phytohemagglutinin. Here, we present, from a genetic perspective, an SCID patient who not only harbored a novel mutation in the gene encoding the common c chain (cc) of the IL-2 receptor (IL2RG), but also carried reactive maternal T lymphocytes that produced a karyotype that was initially perplexing.

Newborn Screening for SCID Identifies Patients with Ataxia Telangiectasia

“…B and NK cell numbers and lymphocyte proliferation were normal, but Vβ spectratyping showed decreased T cell diversity (not shown). As with infant V003, in vitro phosphorylation of STAT5 after IL-2 activation was diminished, but not absent, as would be the case in SCID due to defects in the IL-2 receptor common γ chain or Janus kinase 3 [9, 24]. Physical examination of infant V004 has been normal to date, but she did not mount robust antibody to T-cell dependent protein-conjugated H .…”

“…15 0 . 68 Proliferation to PHAnormalnormalDiversity of TCR Vβ repertoire e normal decreased IL-2 induced STAT5 phosphorylation f 55  % of control 75  % of control a Initial and follow-up dried blood spot samples from infant V003 were incomplete, with low TRECs, but also low β-actin; despite multiple notifications from the newborn screening program, there were delays between the initial screening result and a follow-up blood sample being submitted for both flow cytometry and a third TREC screen, which was positive b Initial screening result from infant V004 was positive at age 16 days; follow-up flow cytometry was performed at age 21 days; this timeline is typical for the CA SCID screening program c Abnormal values displayed in bold type d Serum antibody concentrations following 3 immunizations e Spectratyping according to Sarzotti et al [23] f EBV transformed cells exposed to IL-2, normal control = 100 % [24]…”

“…Low T and B cell numbers persisted, and low IgG levels with failure to produce antibodies after vaccination led to institution of immunoglobulin replacement and trimethoprim-sulfamethoxazole antibiotic prophylaxis. Lymphocyte proliferation to phytohemagglutinin and TCR Vβ diversity assessed by spectratyping [23] were normal, but an Epstein Barr virus transduced B cell line from the patient had only half normal phosphorylation of STAT5 in response to IL-2 [24], suggesting an intrinsic lymphocyte impairment. Later, at age 14–16 months, V003 was reported by her mother to have “unsteady” gait; physical examination first showed mild truncal ataxia at 20 months.…”

A novel IL2RG mutation presenting with atypical T−B+NK+ phenotype: Rapid elucidation of NK cell origin

“…X‐Linked SCID is characterized by early‐onset of severe infections, facilitated by the absence of T and NK lymphocytes (T − B + NK − phenotype) . However, different mutations in the IL‐2RG gene have been reported associated with a phenotype variant T − B + NK + . Here we describe a novel mutation of the IL‐2RG gene consisting of a triple insertion (ACC) at exon 5, in which NK cells were found in peripheral blood, representing a burden for initial patient diagnosis.…”

Retrospective diagnosis of X-linked hyper-IgM syndrome in a family with multiple deaths of affected males

“…Retrospective diagnosis of primary immunodeficiency diseases (PIDs) may be a professional and psychological challenge in X-linked inherited disorders like X-HIGM, 1, 2 X-linked lymphoproliferative disease, 3 X-linked aγ−globulinemia, 4 the Wiskott-Aldrich syndrome, 5 Interleukin-2 receptor gene deficiency, 6 or chronic granulomatous disease (gp91-phox deficiency).…”