Targeted NGS Platforms for Genetic Screening and Gene Discovery in Primary Immunodeficiencies

Conclusions: NGS technology represents a powerful approach in the complex field of rare disorders but its different application should be weighted. A relatively small NGS target panel can be successfully applied for a robust diagnostic suspicion, while when the spectrum of clinical phenotypes overlaps more than one PID an in-depth NGS analysis is required, including also whole exome/genome sequencing to identify the causative gene. Introduction Primary immunodeficiencies (PIDs) are a phenotypically and genetically heterogeneous group of more than 300 monogenic inherited disorders resulting in immune defects that predispose patients to infections, autoimmune disorders, lymphoproliferative disease, and malignancies (1–3). PIDs with a more severe phenotype lead to life-threatening infections and life-limiting complications that require a prompt and accurate diagnosis in order to initiate lifesaving therapy (4, 5). Phenotypic and genotypic heterogeneity of PIDs make genetic diagnosis often complex and delayed. Indeed, more than one genotype might cause similar clinical phenotypes, but identical genotypes will not often produce the same phenotype and finally clinical penetrance may be different (6–9). The characterization of PID-associated genes is expected to significantly contribute to define the molecular events governing immune system development and will provide new insights into the pathogenesis of PIDs. Molecular genetic testing is also a useful tool f...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research