Genetics of Inborn Errors of Immunity in highly consanguineous Middle Eastern and North African populations

• Published in: Seminars in immunology 2023-05, Vol.67, p.101763-101763, Article 101763
• Main Authors: Al-Mousa, Hamoud, Barbouche, Mohamed-Ridha
• Format: Article
• Language: English
• Subjects: Africa, Northern - epidemiology; Agammaglobulinemia; Chronic granulomatous disease; Consanguinity; Genetic; Humans; Immune dysregulation; Immune System Diseases - genetics; Immunodeficiency; Inborn Errors of Immunity; Middle East; Middle Eastern People - genetics; Mutation; North Africa; North African People - genetics; SCID
• ISSN: 1044-5323; 1096-3618
• DOI: 10.1016/j.smim.2023.101763

Consanguineous marriages in Middle Eastern and North African (MENA) countries are deeply-rooted tradition and highly prevalent resulting into increased prevalence of autosomal recessive diseases including Inborn Errors of Immunity (IEIs). Molecular genetic testing is an important diagnostic tool for IEIs since it provides a definite diagnosis, genotype-phenotype correlation, and guide therapy. In this review, we will discuss the current state and challenges of genomic and variome studies in MENA region populations, as well as the importance of funding advanced genome projects. In addition, we will review the MENA underlying molecular genetic defects of over 2457 patients published with the common IEIs, where autosomal recessive mode of inheritance accounts for 76% of cases with increased prevalence of combined immunodeficiency diseases (50%). The efforts made in the last three decades in terms of international collaboration and of in situ capacity building in MENA region countries led to the discovery of more than 150 novel genes involved in IEIs. Expanding sequencing studies within the MENA will undoubtedly be a unique asset for the IEI genetics which can advance research, and support precise genomic diagnostics and therapeutics. •Consanguineous marriages in MENA are prevalent resulting into increased prevalence of autosomal recessive Inborn Errors of Immunity (IEIs).•At least 150 novel IEIs have been discovered through collaborative research from MENA paving the way to improve our knowledge on immune pathways.•More than 2500 patients reported shed light into common underlying genetic defects for IEIs in MENA.•Capacity-building in genetic diagnostic services and genetic counseling expertise that respects common values and cultures is needed.