Heterogeneity in combined immunodeficiencies with associated or syndromic features (Review)

Caba,Lavinia; Gug,Cristina; Gorduza,Eusebiu Vlad

doi:10.3892/etm.2020.9517

Heterogeneity in combined immunodeficiencies with associated or syndromic features (Review)

Authors:
- Lavinia Caba
- Cristina Gug
- Eusebiu Vlad Gorduza
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Affiliations: Department of Medical Genetics, ‘Grigore T. Popa’ University of Medicine and Pharmacy, 700115 Iași, Romania, Department of Microscopic Morphology, ‘Victor Babeş’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
Published online on: November 26, 2020 https://doi.org/10.3892/etm.2020.9517
Article Number: 84
Copyright: © Caba et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Primary immunodeficiencies are genetic diseases, mainly monogenic, that affect various components of the immune system and stages of the immune response. The category of combined immunodeficiencies with associated or syndromic features comprises over 70 clinical entities, characterized by heterogeneity of clinical presentation, mode of transmission, molecular, biological, mutational and immunological aspects. The mutational spectrum is wide, ranging from structural chromosomal abnormalities to gene mutations. The impact on the function of the proteins encoded by the genes involved is different; loss of function is most common, but situations with gain of function are also described. Most proteins have multiple functions and are components of several protein interaction networks. The pathophysiological mechanisms mainly involve: Missing enzymes, absent or non‑functional proteins, abnormal DNA repair pathways, altered signal transduction, developmental arrest in immune differentiation, impairment of cell‑to‑cell and intracellular communications. Allelic heterogeneity, reduced penetrance and variable expressivity are genetic phenomena that cause diagnostic difficulties, especially since most are rare/very rare diseases, which is equivalent to delaying proper case management. Most primary immunodeficiencies are Mendelian diseases with X‑linked or recessive inheritance, and molecular diagnosis allows the identification of family members at risk and the application of appropriate primary and secondary prevention measures in addition to the specific curative ones. In conclusion, recognizing heterogeneity and its sources is extremely important for current medical practice, but also for the theoretical value of improving biological and biomedical applications.

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