Next generation sequencing (NGS)-based approach to diagnosing Algerian patients with suspected inborn errors of immunity (IEIs)

Xiao P Peng; Moudjahed Saleh Al-Ddafari; Andres Caballero-Oteyza; Chahrazed El Mezouar; Pavla Mrovecova; Saad Eddin Dib; Zoheir Massen; Mohammed Chems-Eddine Smahi; Alddafari Faiza; Rafik Terki Hassaïne; Gérard Lefranc; Mourad Aribi; Bodo Grimbacher

doi:10.1016/j.clim.2023.109758

Next generation sequencing (NGS)-based approach to diagnosing Algerian patients with suspected inborn errors of immunity (IEIs)

Clin Immunol. 2023 Nov:256:109758. doi: 10.1016/j.clim.2023.109758. Epub 2023 Sep 9.

Affiliations

¹ Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Germany; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America. Electronic address: xpeng15@jhmi.edu.
² Laboratory of Applied Molecular Biology and Immunology, W0414100, University of Tlemcen, Algeria; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Germany.
³ Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Germany; RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Germany.
⁴ Laboratory of Applied Molecular Biology and Immunology, W0414100, University of Tlemcen, Algeria; Pediatric Department, Medical Center University of Tlemcen, Faculty of Medicine, University of Tlemcen, Algeria.
⁵ Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Germany.
⁶ Pediatric Department, Medical Center University of Tlemcen, Faculty of Medicine, University of Tlemcen, Algeria.
⁷ Laboratory of Applied Molecular Biology and Immunology, W0414100, University of Tlemcen, Algeria; Specialized Mother-Child Hospital of Tlemcen, Department of Neonatology, Faculty of Medicine, University of Tlemcen, Algeria.
⁸ Department of Internal Medicine, Medical Center University of Tlemcen, Faculty of Medicine, University of Tlemcen, Tlemcen, Algeria.
⁹ Pediatric Hospital Canastel, Faculty of Medicine, University of Oran, Algeria.
¹⁰ Institute of Human Genetics, UMR 9002 CNRS-University of Montpellier, France.
¹¹ Laboratory of Applied Molecular Biology and Immunology, W0414100, University of Tlemcen, Algeria. Electronic address: mourad.aribi@univ-tlemcen.dz.
¹² Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Germany; DZIF - German Center for Infection Research, Satellite Center Freiburg, Germany; CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany; RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Germany. Electronic address: bodo.grimbacher@uniklinik-freiburg.de.

PMID: 37678716
DOI: 10.1016/j.clim.2023.109758

Abstract

The advent of next-generation sequencing (NGS) technologies has greatly expanded our understanding of both the clinical spectra and genetic landscape of inborn errors of immunity (IEIs). Endogamous populations may be enriched for unique, ancestry-specific disease-causing variants, a consideration that significantly impacts molecular testing and analysis strategies. Herein, we report on the application of a 2-step NGS-based testing approach beginning with targeted gene panels (TGPs) tailored to specific IEI subtypes and reflexing to whole exome sequencing (WES) if negative for Northwest Algerian patients with suspected IEIs. Our overall diagnostic yield of 57% is comparable to others broadly applying short-read NGS to IEI detection, but data from our localized cohort show some similarities and differences from NGS studies performed on larger regional IEI cohorts. This suggests the importance of tailoring diagnostic strategies to local demographics and needs, but also highlights ongoing concerns inherent to the application of genomics for clinical IEI diagnostics.

Keywords: Ancestry; Diversity; Expressivity; Genetic paradigms; Inborn errors of immunity; Molecular medicine; Next-generation sequencing; Penetrance; Targeted gene panels; Variant classification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Exome Sequencing
Genomics*
High-Throughput Nucleotide Sequencing*
Humans