WHAT GENE IS AFFECTED TO CAUSE SCID ACTIVATOR
WHAT GENE IS AFFECTED TO CAUSE SCID FREE

3) demonstrated absence of IL2RG, suggesting that the mutation caused degradation of the molecule. 2), we investigated the expression of members of the IL2/JAK3 signaling pathway by western blot. Since the mutation causes a 42 amino acid truncation of the intracellular domain of the γC, including of the Janus kinase 3 (JAK3) binding site (Fig.

Based on this finding, the therapeutic plan of the patient was changed and he became a potential candidate for allogeneic hematopoietic stem cell transplantation. Comparing with the primary immunodeficiency genes database, the only variant consistent with the patient’s immunological phenotype was a novel nonsense mutation, p.R328X (c.982C>T) in exon 8 of the IL2RG gene (Fig. Analysis of all variants were performed according to a standard pipeline described previously we identified 2 homozygous (autosomal) and 5 hemizygous (X-linked) variants which were absent from dbSNP database and 1000 Genome database (Additional file 1: Table S1). As the patient was born in a consanguineous family and showed a family history of recurrent infections and early death on the maternal side, an autosomal recessive or X-linked inheritances pattern was expected. In order to identify the molecular defect, whole exome sequencing (WES) was performed.

WHAT GENE IS AFFECTED TO CAUSE SCID FREE

Despite his combined immunodeficiency, the patient was free from opportunistic infections and his condition improved with temporary substitution of subcutaneous immunoglobulin and prophylactic antibiotics. The observation suggested that PHA and ConA stimulations for CD4 + T cells may be different from CD8 + T cells. However, normal response to mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) by CD4 + T cells, but not CD8 + T cells were detected. The patient had low specific cell-mediated immune response in activated whole blood using mitogens and antigen, such as pokeweed mitogen (PWM), candida antigen etc. Low CD4 + and CD8 + T cell numbers, with normal numbers of B and NK cells were detected (Fig. Although a complete blood count and immunoglobulin levels were normal, lymphocyte populations were measured. Immunologic profiles were investigated as previously described. Here we describe a novel nonsense mutation in the IL2RG gene consisting of a single nucleotide substitution at exon 8, in which a normal count of NK cells was found in peripheral blood.Īt the age of 8 years, a computed tomography was performed due to a progression of his pulmonary disease which revealed bronchiectasis and a right middle lobe atelectasis. ĭue to poorly defined clinical and immunological phenotypes, the diagnosis is usually established later in childhood or even in adulthood, and the appropriate treatment is thus delayed. In addition, some of these patients might not be detected by newborn screening programs for SCID.

Some patients might be less susceptible to infections, the reduction of T cells is relatively moderate and a normal lymphocyte proliferation assay may be observed. Several patients having hypomorphic IL2RG mutation with a milder form of combined immunodeficiency, termed “atypical X-SCID”, have been described previously. The disease is usually lethal within the 1st year of life unless reconstitution of the immune system is carried out.ĭifferent mutations in the IL2RG gene have also been shown to be associated with less severe phenotypic variants. Additional features include protracted diarrhea, rash, fever, pneumonia and sepsis. Infants with X-SCID are highly susceptibility to bacterial and opportunistic infections. In typical X-SCID, the disease is characterized by an almost complete absence of T and NK cells, and nearly normal or high numbers of functionally deficient B cells (T –B +NK − phenotype). The variability in the phenotypic spectrum of classic X-SCID associated gene highlights the necessity of multi-disciplinary cooperation vigilance for a more accurate diagnostic workup.

This is the first report of an atypical X-SCID phenotype due to an exon 8 mutation in the IL2RG gene. In addition, the characteristics of the mutations previously described in 39 patients with an atypical phenotype were reviewed and analyzed from the literature.

WHAT GENE IS AFFECTED TO CAUSE SCID ACTIVATOR

Functional impairment of the IL2RG was confirmed by IL2-Janus kinase 3-signal transducer and activator of transcription signaling pathway investigation.

We report a 16-year-old patient with a T low B + NK + cellular immunodeficiency due to a novel nonsense mutation in exon 8 (p.R328X) of the IL2RG gene. Due to a leaky clinical phenotype, diagnosis and appropriate treatment are challenging in these patients. Atypical X-linked severe combined immunodeficiency (X-SCID) is a variant of cellular immunodeficiency due to hypomorphic mutations in the interleukin 2 receptor gamma ( IL2RG) gene.

What gene is affected to cause scid