SCIENTIFIC BACKGROUND

ADA, AK2, CD247, CD3D, CD3E, CD3G, CD40, CD40LG, CD8A, CIITA, CORO1A, DCLRE1C, DOCK8, FOXN1, IKZF1, IL2RG, IL7R, ITK, JAK3, LCK, LIG4, MAGT1, NHEJ1, ORAI1, PNP, PRKDC, PTPRC, RAG1, RAG2, RFX5, RFXANK, RFXAP, RHOH, RMRP, STAT5B, STIM1, STK4, TAP1, TAP2, TAPBP, UNC119, ZAP70

Category:

Scientific Background

Combined immunodeficiencies (CID), including severe combined immunodeficiencies (SCID), are a heterogeneous group of genetic diseases characterized by a deficiency in and/or a malfunction of T cells. In SCID, a distinction is made between diseases that also have a reduced number of circulating B cells (T-B-SCID, about 35% of SCID patients) and SCID forms in which B cells are present (T-B+SCID, about 65% of SCID patients), although B cell function is always impaired (even where there is normal development of these cells) due to the lack of T cell help for the antibody response. In addition, the number of NK cells may be reduced. While in CID, residual functions of the immune system remain intact and CID patients can be relatively healthy, SCID is lethal without a blood stem cell transplant before the age of two. Clinical manifestations of SCID usually occur within the first 6 months of life. They are usually protracted infections of the gastrointestinal tract and respiratory tract, severe varicella, complicated EBV, CMV or adenovirus infections or persistent thrush. In some cases, the persistence of maternal T cells, which are not rejected and can proliferate in SCID patients, can lead to symptoms of graft-versus-host disease (GvHD).

 

SCID disease mainly affects genes whose products are involved in the maturation of lymphocytes. These include cytokine receptors and their signal-transducing molecules, which are essential for the early differentiation and maturation of lymphocytes, as well as proteins that are necessary for the formation and function of B and/or T cell receptors. The most common form of SCID is caused by mutations in the IL2RG gene on the X chromosome and accounts for about 80% of SCID cases in male patients. Other more frequently affected genes (autosomal recessive) are RAG1/RAG2, DCLRE1C (Artemis), ADA and JAK3 (in total up to 40% of all SCID cases). Hypomorphic mutations in SCID-typical genes, which allow residual function of the affected protein, can lead to atypical SCID, where the clinical phenotype is currently not clearly defined. The course of the disease is not as severe as in typical SCID, and the diagnosis should also be considered in older children and even in adult patients. Hypomorphic mutations in some SCID-associated genes can lead to Omenn syndrome (OS), an inflammatory disease similar to GvHD. In addition to typical SCID symptoms, OS patients show additional inflammatory symptoms such as lymphadenopathy, hepatosplenomegaly, generalized erythroderma and alopecia. The use of NGS for the simultaneous analysis of CID/SCID-relevant genes (gene panel diagnostics) can be helpful in making an early genetic diagnosis.

 

References

Bousfiha et al. 2018, J Clin Immunol 38:129 / Picard et al. 2018, J Clin Immunol 38:96 / Routes et al. 2014, J Clin Immunol 34:398 / Felgengreff et al. 2011, Clin Immunol 141:73 / Fischer et al. 2005, Immunol Rev 203:98 / Buckley et al. 2004, Annu Rev Immunol 22:625 / Muller et al. 2001, Blood 98:1847

GENES

ADA, AK2, CD247, CD3D, CD3E, CD3G, CD40, CD40LG, CD8A, CIITA, CORO1A, DCLRE1C, DOCK8, FOXN1, IKZF1, IL2RG, IL7R, ITK, JAK3, LCK, LIG4, MAGT1, NHEJ1, ORAI1, PNP, PRKDC, PTPRC, RAG1, RAG2, RFX5, RFXANK, RFXAP, RHOH, RMRP, STAT5B, STIM1, STK4, TAP1, TAP2, TAPBP, UNC119, ZAP70

ASSOCIATED TESTS

How to order

LATEST ARTICLES

Cancer is a group of genetic diseases that can develop almost anywhere in the body. Many people in the world are affected by cancer every year. Follo...

Read more

Aiming to evaluate the role of chromosomal aneuploidy in pregnancy loss, a 2023 study 35 years in the making evaluated the genomic landscape of first...

Read more

Cancer is a complex genetic disease that affects millions of people in the world. It is one of the leading causes of death worldwide, with about ten ...

Read more

Researchers created a detailed map of the placenta during labor. By studying how maternal and fetal cells communicate, they discovered signals in the...

Read more

A recent paper published in Nature Medicine (1) aimed to identify genes and genomic biomarkers which can better predict outcomes and personalized the...

Read more

In honor of the international day of women and girls in science, we interviewed one of our very own, Dr. Evelina Papaioannou. Dr. Evelina Pa...

Read more

Aneuploidies, such as translocations, whole or segmental chromosomal duplications, and deletions, are examples of chromosomal abnormalities that are ...

Read more

Here you can read the winning essays from the first, annual DNA essay competition on the subject of "How unfolding the DNA code can help with precisi...

Read more

Introduction Our voices are as unique as our fingerprints! Although there are people whose voices might sound alike, there are no two voices exact...

Read more

Not everyone likes winter. For people who do not enjoy the cold weather, or having to put on a thick coat to go outside, a winter can be a source of ...

Read more