# Defects in Innate and Intrinsic Immunity in Morocco: A Retrospective Analysis of the Genetic Landscape and Clinical Correlations

## TL;DR

This study explores genetic causes of immune deficiencies in Morocco, showing how early genetic testing can improve diagnosis and treatment for patients with rare immune disorders.

## Contribution

The study identifies novel genetic variants and highlights the prevalence of specific immune disorders in the Moroccan population.

## Key findings

- MSMD and CMC are notably prevalent in Moroccan patients with innate immune deficiencies.
- Novel genetic variants, such as IRAK4 c.277delT and SNORA31 n.36T>C, were identified in Moroccan patients.
- Early genetic screening is shown to be valuable for accurate diagnosis and improved patient outcomes.

## Abstract

Susceptibility to common infectious diseases is often linked to innate immune deficiencies. Patients may present normal standard immunological profiles but remain highly vulnerable to infections, complicating diagnosis. This study investigates innate and intrinsic immune deficiencies and their genetic underpinnings in Moroccan patients, emphasizing early detection and personalized care.

A retrospective analysis was conducted using data from the Moroccan Inborn Errors of Immunity (IEI) registry (2008–2024). Included were patients with confirmed innate or intrinsic immunodeficiencies based on CBC, CRP, immunoglobulin levels, lymphocyte subpopulations, and whole-exome sequencing. Classification followed the 2022 IUIS criteria.

Among 884 patients with IEI, 79 (∼9%) had innate or intrinsic immunodeficiencies, with genetic confirmation in 46 (58%). Of these, 23 (50%) were diagnosed with Mendelian susceptibility to mycobacterial disease (MSMD), involving mutations in the IL12RB1, STAT1, IFNGR1, SPPL2A, TYK2, and TBX21 (T-bet) genes. Chronic mucocutaneous candidiasis (CMC) was found in 15 (32%) patients, linked to STAT1 and IL17RA mutations. Severe viral infection predisposition was seen in 3 patients (POLR3A, IFIH1, TLR7XL) and bacterial susceptibility in 3 others (IRF4, IFNGR1, NCSTN). Novel variants were identified, including IRAK4 c.277delT (p.F93fsX26), not previously reported, and SNORA31 (n.36T>C), previously seen in Saudi Arabia, now found in a Moroccan case of herpes simplex encephalitis.

This study reveals the genetic complexity of innate immune disorders in Morocco, with a notable prevalence of MSMD and CMC. It underscores the value of early genetic screening to guide diagnosis and improve patient outcomes.