A novel common gamma chain mutation in a Chinese family with X-linked severe combined immunodeficiency (X-SCID; T−NK−B+)

Abstract

X-linked severe combined immunodeficiency (X-SCID) is one of the most common causes of primary immunodeficiencies in humans. A 4-month-old boy with recurrent pulmonary infection had decreased numbers of CD3(+), CD4(+), CD8(+) T lymphocytes, and NK cells and increased levels of CD19(+) B cells but no memory B cells or plasma cells. The production of cytokines by T cells and the activation of T and B cells were either absent or inefficient. While B cell levels were high, they were all IgM-positive, and the secretion of all Ig isotypes by activated B cells in vitro was defective. Genomic DNA sequencing revealed that the patient had missense mutations in the IL2RG (exon 5, 718 T > C) and IL7R genes (exon 2, 197 T > C; exon 4, 412G > A). Although the patient's father and one of his sisters have the same missense homozygous mutations of the IL7R gene, neither of them exhibited the immunological phenotype of SCID. The results indicate that the IL2RG gene mutation or a combination of the IL7R and IL2RG mutations in the sick boy had resulted in T(-)NK(-)B(+) SCID.

Il7r Gen Mutasyon Ve Poli̇morfi̇zmlari̇ni̇n Ağir Kombi̇ne İmmun Yetmezli̇kli̇ Hastalardaki̇ Sikliği

“…Çin'in değişik bölgelerinde ağır kombine immün yetmezlikli hastalarda mutasyon taraması yapılmış ve ülkede IL7R mutasyonun yaygın olduğu tespit edilmiştir (Tan, Yu & Lei, 2015;Wang, Wen & Zhen, 2014).…”

A Novel RAG1 Mutation in a Compound Heterozygous Status in a Child With Omenn Syndrome

“…Immunoglobulin expression on B cells was also investigated (Tan et al, 2015). The levels of both IgG and IgM expression were considerably lower in the patient than in other family members ( Figure 3B ).…”

“…Cytokine production by peripheral blood mononuclear cells from the patient and the healthy child was evaluated (Tan et al, 2015). Peripheral blood mononuclear cells were stimulated with or without phorbol myristate plus ionomycin for 24 h. Following stimulation, the supernatant was harvested, and the levels of interferon gamma (IFN-γ), tumor necrosis factor (TNF-α), interleukin (IL)-2, IL-4, IL-17, and IL-21 were detected by cytometric bead array ( Figure 4B ).…”

Uses of Next-Generation Sequencing Technologies for the Diagnosis of Primary Immunodeficiencies

“…Receptor activation can be assessed by the phosphorylation of downstream proteins or upregulation of target gene expression (60). Mutations in genes important for lymphocyte activation can be evaluated by assessing upregulation of activation markers, quantifying proliferation in response to mitogens and antigen stimulation, and measure the secretion of cytokines and immunoglobulins after T or B cell activation, respectively (61). Cellular modeling requires the use of patient-derived cells that may not be readily available.…”