APPLICATION OF GENOMICS FOR THE PRECISION DIAGNOSIS OF INBORN ERRORS OF IMMUNITY

Abstract

Primary immunodeficiencies (PIDs), also called “Inborn Errors of Immunity (IEI)”, are monogenic inborn defects of the immune system that result in immunodeficiencies and/or immunological dysregulation. The main clinical manifestations of PIDs are severe allergies, autoimmunity, inflammation, increased susceptibility to infections, as well as malignancy. Hyper-IgE syndromes (HIES) are one of the many genetically inherited PID categories that have been identified over the years. HIES are characterized by persistent skin abscesses, dermatitis, allergies, and pulmonary infections, as well as high serum IgE levels. Both, autosomal dominant (AD) and recessive (AR) forms of the disease have been reported. PIDs are individually rare, however, they are collectively much more common due to new phenotypes and new genotypes being discovered rapidly. Also, in countries with high rates of consanguinity and large family sizes like Qatar, a higher prevalence, in particular of autosomal recessive cases, is observed. We made an effort to understand the molecular and genetic foundation of PIDs by using whole genome sequencing data analysis of the patients and their families recruited from Qatar. The goal of this study was to discover novel disease-causing variants in the patient's DNA, and to understand the mechanisms of impairing the human immune system at the cellular and molecular levels by these genetic variants. Within our study group, we were able to identify novel, rare variants that may contribute to our understanding of genetic PID causes, particularly Hyper IgE syndrome. This research is a prime example of how genomics and such high throughput technologies can be used to diagnose diseases related to PID and implement precision medicine.

Date of Award	2024
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences