Clinical exome sequencing data from patients with inborn errors of immunity : Cohort level diagnostic yield and the benefit of systematic reanalysis

Détails bibliographiques
Publié dans:	Clinical immunology (Orlando, Fla.). - 1999. - 268(2024) vom: 04. Nov., Seite 110375
Auteur principal:	Vorsteveld, Emil E (Auteur)
Autres auteurs:	Van der Made, Caspar I (Autre), Smeekens, Sanne P (Autre), Schuurs-Hoeijmakers, Janneke H (Autre), Astuti, Galuh (Autre), Diepstra, Heleen (Autre), Gilissen, Christian (Autre), Hoenselaar, Evelien (Autre), Janssen, Alice (Autre), van Roozendaal, Kees (Autre), Engelen, Jettie Sikkema-van (Autre), Steyaert, Wouter (Autre), Weiss, Marjan M (Autre), Yntema, Helger G (Autre), Mantere, Tuomo (Autre), AlZahrani, Mofareh S (Autre), van Aerde, Koen, Derfalvi, Beata, Faqeih, Eissa Ali, Henriet, Stefanie S V, van Hoof, Elise, Idressi, Eman, Issekutz, Thomas B, Jongmans, Marjolijn C J, Keski-Filppula, Riikka, Krapels, Ingrid, Te Loo, Maroeska, Mulders-Manders, Catharina M, Ten Oever, Jaap, Potjewijd, Judith, Sarhan, Nora Tarig, Slot, Marjan C, Terhal, Paulien A, Thijs, Herman, Vandersteen, Anthony, Vanhoutte, Els K, van de Veerdonk, Frank, van Well, Gijs, Netea, Mihai G, all members of the Radboud University Medical Center multidisciplinary immune-disease board, Simons, Annet, Hoischen, Alexander, Arts, Rob J W, Bijker, Else M, Bruno, Mariolina, Hobo, Willemijn, Hoppenreijs, Esther, de Jonge, Marien I, van Laarhoven, Arjan, van der Molen, Renate, Oud, Manon, Schatorje, Ellen J H, Smeets, Ruben, Sprenkeler, Evelien G G, Stol, Kim, Verhagen, Lilly M, Zonneveld-Huijssoon, Evelien
Format:	Article en ligne
Langue:	English
Publié:	2024
Accès à la collection:	Clinical immunology (Orlando, Fla.)
Sujets:	Journal Article Autoimmune disorders Autoinflammatory disorders Clinical exome sequencing Exome reanalysis Genomics Inborn errors of immunity Longitudinal follow-up NGS-based sequencing Primary immunodeficiencies

Description
Résumé:	Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated in silico IEI gene panel. Variants were classified and curated through expert review. The molecular diagnostic yield after standard exome analysis was 11.8 %. Through systematic reanalysis, we identified variants of interest in 5.2 % of undiagnosed patients, with 76.7 % being (candidate) disease-causing, providing a (candidate) diagnosis in 15.2 % of our cohort. We find a 1.7 percentage point increase in conclusive molecular diagnoses. We find a high degree of actionability in patients with a genetic diagnosis (76.4 %). Despite the modest absolute diagnostic gain, these data support the benefit of iterative exome reanalysis in IEI patients, conveying the notion that our current understanding of genes and variants involved in IEI is by far not saturated
Description:	Date Completed 04.11.2024 Date Revised 04.11.2024 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-7035
DOI:	10.1016/j.clim.2024.110375