Next-Generation Sequencing in the Field of Primary Immunodeficiencies: Current Yield, Challenges, and Future Perspectives
SourceClinical Reviews in Allergy and Immunology, 61, 2, (2021), pp. 212-225
Article / Letter to editor
Display more detailsDisplay less details
Clinical Reviews in Allergy and Immunology
SubjectRadboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences
Primary immunodeficiencies comprise a group of inborn errors of immunity that display significant clinical and genetic heterogeneity. Next-generation sequencing techniques and predominantly whole exome sequencing have revolutionized the understanding of the genetic and molecular basis of genetic diseases, thereby also leading to a sharp increase in the discovery of new genes associated with primary immunodeficiencies. In this review, we discuss the current diagnostic yield of this generic diagnostic approach by evaluating the studies that have employed next-generation sequencing techniques in cohorts of patients with primary immunodeficiencies. The average diagnostic yield for primary immunodeficiencies is determined to be 29% (range 10-79%) and 38% specifically for whole-exome sequencing (range 15-70%). The significant variation between studies is mainly the result of differences in clinical characteristics of the studied cohorts but is also influenced by varying sequencing approaches and (in silico) gene panel selection. We further discuss other factors contributing to the relatively low yield, including the inherent limitations of whole-exome sequencing, challenges in the interpretation of novel candidate genetic variants, and promises of exploring the non-coding part of the genome. We propose strategies to improve the diagnostic yield leading the way towards expanded personalized treatment in PIDs.
This item appears in the following Collection(s)
- Academic publications 
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.