Practical Approach to Genetic Testing for Primary Immunodeficiencies.

Abstract Allergy and immunology practitioners are often consulted to evaluate patients with primary immune deficiency disorders (PIDD), in part because of improved awareness and diagnostic evaluation of these once considered rare diseases. This Yardstick provides information regarding state-of-the-art genetic testing to assist in the evaluation of patients with suspected or confirmed immunodeficiencies. Advances in gene sequencing technology has led to increased accessibility to genetic testing, which is essential for diagnosis, treatment, prognosis, and reproductive/family counseling. Methods that allow simultaneous sequence of several genes, known as targeted gene. sequencing (TGS), whole exome sequencing (WES), and whole genome sequencing (WGS), are currently being offered by clinical laboratories. Fluorescent in situ hybridization (FISH) and chromosomal microarray (CMA) are used to detect duplications or deletions of chromosomal regions. Each of these methods has advantages and disadvantages in the diagnostic workup of PIDD. Counseling on genetic implications to patients and their families is necessary before and after test results are available. Interpretation of results requires understanding of both genetic and immunological mechanisms of disease, especially when a newly described gene variant is reported and its association with disease has not been previously demonstrated.