Only about 28% of US patients with suspected inborn errors of immunity ever get genetic testing — and even exome or genome sequencing finds the answer in only 30-40% of cases. In JACI: In Practice, Yang, Chinn, Orange and Peng offer a practical guide to doing better.
Their main points: keep the threshold low, but test when the result could change management. Phenotype first — history, exam and functional immune assays should drive the choice of test. And the biggest test is not always the best: a targeted panel often beats an exome when the phenotype points to one pathway.
Expect uncertainty, too. Variants of uncertain significance are common, and many patients wait over a decade for a diagnosis. Counsel before you order, and plan to reinterpret results over time.
References:
Yang R, et al. J Allergy Clin Immunol Pract. 2026;14(10):2200-2208.e6.
https://doi.org/10.1016/j.jaip.2026.06.034