Toward universal screening for disease-causing alleles: Mendelian susceptibility to mycobacterial disease as a model.

Advances in genomic technologies, including whole exome and genome sequencing, have transformed diagnosis of monogenic disorders such as inborn errors of immunity (IEIs). In high-consanguinity populations like the United Arab Emirates (UAE), where autosomal recessive disorders are prevalent, early genomic screening shifts care from reactive diagnosis to personalized care. UAE national programs remain limited to premarital or neonatal panels, missing disorders with variable onset or incomplete penetrance. We advocate universal genomic screening to integrate disease-causing alleles into clinical care. As proof of concept, we highlight Mendelian susceptibility to mycobacterial disease (MSMD), an IEI defined by impaired interferon-gamma signaling and severe complications following Bacillus Calmette-Guérin (BCG) vaccination and Mycobacterium tuberculosis disease. We propose a tiered approach using MSMD-related genes within exome or genome platforms, enabling scalable, cost-effective implementation and periodic reanalysis as evidence evolves. In the UAE, high consanguinity, genomic infrastructure, and regulatory frameworks position MSMD as an entry point for population genomic screening, advancing precision medicine and prevention.