Published Online: February 23, 2016
Molecular genetic testing became an essential diagnostic tool for primary immunodeficiency diseases (PIDs). The clinical and immunological characteristic of affected patients guides selection of gene(s) to be tested. However, candidate gene selection is not a straightforward task given that several genes can be responsible for a disease and moreover the same gene defect can present with different clinical presentation. A promising solution to overcome the complications associated with the molecular genetic diagnosis of PIDs is the use of targeted next generation sequencing (NGS), where a panel of selected genes of interest is screened to identify the genetic defect.
In a study recently published in The Journal of Allergy and Clinical Immunology (JACI), Al-Mousa and colleagues studied the utility of targeted next generation sequencing of a comprehensive primary immunodeficiency panel that contains 162 PID genes in 261 patients with variable PIDs.
The researchers included 122 PID patients with known mutations in order to validate the assay. It was able to detect the mutation in 117 out of 122 (96%). Another 139 patients suspected of having PIDs, but without a confirmed genetic diagnosis were included, most of them had previous extensive genetic studies based on a candidate gene approach. The assay resulted in a molecular genetic diagnosis for 35 of 139 patients. Interestingly, most of these cases represented atypical clinical presentations of known PIDs that were unlikely to be diagnosed based on classical approach.
The authors concluded that this approach can be used as a first line diagnostic assay, reduces the cost, eases interpretative challenges and speeds up diagnosis for the majority of PID cases.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.