Studying innate immune deficiencies is crucial for understanding susceptibility to common infections, as affected patients often have normal immunological profiles yet face diagnostic challenges. This study examines genetic variations in Moroccan patients, emphasizing the need for early detection and treatment.
This is a retrospective study (2008–2024) that analyzed Moroccan IEI registry patients with innate and intrinsic immunodeficiencies, confirmed through CBC, CRP, immunoglobulin levels, lymphocyte subpopulation analysis, and whole-exome sequencing (WES), following the 2022 IUIS classification.
This study highlights the genetic diversity of innate and intrinsic immune deficiencies in Moroccan patients, with Mendelian susceptibility to mycobacterial disease (MSMD) and chronic mucocutaneous candidiasis (CMC) being the most prevalent conditions. Among the 79 patients studied, 46 (58%) had a confirmed genetic diagnosis, with IL12RB1, STAT1, IFNGR1, SPPL2A, TYK2, and TBX21 mutations identified in MSMD cases, and STAT1 and IL17RA mutations linked to CMC. Additionally, three cases of severe viral infection predisposition were linked to a POLR3A, IFIH1, and TLR7XL variation and three cases of bacterial infection predisposition were linked to IRF4, IFNGR1, and NCSTN variation were detected. Notably, a novel IRAK4 mutation (c.277delT, p. F93fsX26) and the SNORA31 variant previously reported in a Saudi Arabian patient were identified. High consanguinity (51.1%) and delayed genetic diagnosis (21–51 months) were observed, emphasizing the need for early genetic screening. These findings underscore the importance of cost-effective diagnostic methods, such as PCR-based genetic screening, to improve early detection and optimize clinical management in Morocco.
This study identifies novel and recurrent mutations in Moroccan patients with innate immune defects, highlighting the high prevalence of MSMD and CMC. The findings underscore the need for early genetic screening to improve disease awareness, early detection, and patient outcomes.
