SCID Essay

Mutations of the GL13 gene during development is known to cause this disorder. It is known to be involved in the patterning of tissues and organs. It helps by helping to control whether specific genes are turned off or on. This condition can also be inherited.

Hyper-IgE syndrome occurs because of the mutations in STAT3 gene where this gene is important to provide instructions in making proteins. The mutations were either missense

Many different mutations are can be responsible for development of ALD. “more than 1,200 ABCD1 gene mutations

Most people with Smith-Magenis syndrome (SMS) have a deletion of genetic material from a specific region of chromosome 17.The deletion is not usually inherited, occurring randomly during the formation of egg or sperm cells in a parent, or in early embryonic development. In rare cases, the deletion may occur due to a parent having a chromosomal balanced translocation. Although the deleted region contains multiple genes, researchers believe that the loss of the RAI1 gene is responsible for most of the features of SMS. The loss of other genes in the deleted region may explain why the features may vary from person to person. (Rare Diseases) Most

The first X-SCID gene therapy trial used a moloney murine viral vector with the c transgene in two patients with X-SCID. One patient had a missense mutation in IL2RG which resulted in a receptor in the cellular membrane but without a cytoplasmic tail and therefore not functional. The other patient had a frameshift IL2RG mutation which deleted exon 6 and resulted in a truncated receptor that was not expressed on the membrane. Their CD34+ T cells were removed and transfected for three days, at which point they were infused back in to the patient. Around 40% of the infused cells contained the transgene. 15 days after transfusion, circulating T cells containing the transgene were able to be detected circulating in both patients by PCR. The

Recently, a new mutational mechanism leading to increase in number of CAG repeated triplets in several human genes responsible for the hereditary disorders was identified [Caskey et al., 1992; Richards et al., 1992]. The cause of disease is expansion of trinucleotide repeat in the androgen receptor (AR) gene on X chromosome at the Xq11^12 (La Spada et al. 1991). The principal pathological manifestation of the SBMA is loss of the motor neurons in spinal cord and the brainstem (Sobue et al. 1989).

Adaptive immunity develops after exposure to agents such as microbes, toxins or other foreign substances. Adaptive response is a highly specific response that relies on two types of lymphocytes; T cells that mature in thymus and B cells that mature in the bone marrow. The B-cell receptor or BCR is a transmembrane receptor protein located on the outer surface of B cells. The receptor's binding moiety is

The researchers were able to show that MGC1203 is involved in BBS in several ways. They noticed that this protein was the only protein to be present in two separate data sets in which they were identifying proteins that interacted with BBS genes in yeast. 3 MGC1203 was also found in similar locations as the BBS genes in tissues that are often affected by the disorder. They saw that of a group of patients with BBS, 6.2 percent had the 430T variation as compared to only 1.4 percent in the control group, showing a strong correlation between BBS and the 430T variant of MGC1203. They then discovered that five patients had two mutations on a locus for BBS, and also found one parent that was homozygous for 430T that was unaffected. This showed that MGC1203 mutations do not cause the BBS disorder, but show that the 430T mutation influences BBS genes. Ultimately, the researchers concluded that slight mutations to this protein can contribute to the BBS disorder epistatically, by modifying BBS genes in patients that already have a genetic background for the disorder. The 430T allele will change the use of a splice junction, resulting in improper use of exons. This that leads to a loss in a message sent by MGC1203, modifying the penetrance and expressivity of BBS genes. These interactions have a strong contribution in the severity of phenotypes between various BBS

In the disease the NF1 gene is located on the long arm of chromosome 17. Overall when considering an affected

Burney, Davies, Jane C, Tabinda J 2007, NCBI, The application of clinical genetics, Vol.5, pp.29-36

The activated JAK2 kinases phosphorylate signal transducers and activators of transcription (STATs), which activates transcription factors downstream (Rane 2000, Schindler 1995). The transcription factors pair to form a dimer and subsequently migrate to the nucleus to activate the gene transcription (Ni 2004). As a result, the proteolytic cascade initiated by the IL-6/IL-6R complex up-regulates inflammatory mediators and innate immune responses and regulates the expression of genes involved in inflammation, apoptosis, and oxidative stress (Erta 2012, Sacca 2017).

In addition to the hybrid phenotypes co-expressing two lineage specifying T cells, we also obtained phenotypes with the activity of more than two TFs, i.e., Th1-Th2-Treg, Th1-Th17-treg, and Th1-Th2-Th17-Treg. It was shown previously that the basal levels of Tbet and GATA3 can be expressed by subset of Treg cells and the dynamic balance of these TFs helps in maintaining immune tolerance (Yu et al., 2015). Here, we predict the novel phenotypes that can activate three TFs (Tbet-GATA3-Foxp3, Tbet-RORγt-Foxp3) and all four TFs (Tbet-GATA3-RORγt-Foxp3). However, in these phenotypes Tbet and GATA3 have the higher activity levels than the activity levels of Foxp3.

Notwithstanding the concern, Jα18−/−mice has practically still remained as a primary tool for understanding the functional relevance of type II NKT cells.

In most cases, the cause of CVID is undetermined. However, for 10% of cases, the genetic cause of CVID has been identified. Numerous mutations in genes responsible for the function and maturation of immune cells have been associated with the development of CVID, including

This pathway has been associated with several monogenic diseases like the ‘bubble boy’ syndrome (X-linked severe combined immunodeficiency). The extreme susceptibility to pathogens observed is caused by a lack of T and NK cells, which occurs due to loss of function variants of the common γ chain signal transduction. A subset of SCID patients demonstrated mutations in Jak3 kinase specifying the non-redundant in vivo functions for any JAK/STAT component (9). After the initial discovery of JAK3-SCID, many Mendelian disorders were reported. Discoveries made in the past three decades help us to correlate loss of function STAT mutations with specific types of pathogens. STAT1 mutations make patients vulnerable to viral and mycobacterial infections, whereas patients having STAT2 mutations are prone to viral infections and fungal infections are most common in patients with STAT3 mutations (2).