Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies
Files
(Published version)
Date
2019
Authors
Arts, P.
Simons, A.
Alzahrani, M.S.
Yilmaz, E.
Hoischen, A.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Genome Medicine, 2019; 11(1, article no. 38):1-15
Statement of Responsibility
Conference Name
Abstract
Background: Diagnosis of primary immunodeficiencies (PIDs) is complex and cumbersome yet important for the clinical management of the disease. Exome sequencing may provide a genetic diagnosis in a significant number of patients in a single genetic test.Methods: In May 2013, we implemented exome sequencing in routine diagnostics for patients suffering from PIDs.This study reports the clinical utility and diagnostic yield for a heterogeneous group of 254 consecutively referred PID patients from 249 families. For the majority of patients, the clinical diagnosis was based on clinical criteria including rare and/or unusual severe bacterial, viral, or fungal infections, sometimes accompanied by auto immunemanifestations. Functional immune defects were interpreted in the context of aberrant immune cell populations,aberrant antibody levels, or combinations of these factors.Results: For 62 patients (24%), exome sequencing identified pathogenic variants in well-established PID genes. An exome-wide analysis diagnosed 10 additional patients (4%), providing diagnoses for 72 patients (28%) from 68 families altogether. The genetic diagnosis directly indicated novel treatment options for 25 patients that received a diagnosis (34%). Conclusion: Exome sequencing as a first-tier test for PIDs granted a diagnosis for 28% of patients. Importantly, molecularly defined diagnoses indicated altered therapeutic options in 34% of cases. In addition, exome sequencing harbors advantages over gene panels as a truly generic test for all genetic diseases, including in silico extension of existing gene lists and re-analysis of existing data
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
Copyright 2019 The Author(s). (http://creativecommons.org/licenses/by/4.0/)
Access Condition Notes: Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.