Journal article
A novel targeted amplicon Next-Generation sequencing gene panel for the diagnosis of common variable immunodeficiency has a high diagnostic yield
The Journal of Molecular Diagnostics, Vol.24(6), pp.586-599
2022
Abstract
With the advent of next-generation sequencing (NGS), monogenic forms of common variable immunodeficiency (CVID) have been increasingly described. Our study aimed to identify disease-causing variants in a Western Australian CVID cohort using a novel targeted NGS panel. Targeted amplicon NGS was performed on 22 unrelated subjects who met the formal European Society for Immunodeficiencies–Pan-American Group for Immunodeficiency diagnostic criteria for CVID and had at least one of the following additional criteria: disease onset at age <18 years, autoimmunity, low memory B lymphocytes, family history, and/or history of lymphoproliferation. Candidate variants were assessed by in silico predictions of deleteriousness, comparison to the literature, and classified according to the American College of Medical Genetics and Genomics–Association for Molecular Pathology criteria. All detected genetic variants were verified independently by an external laboratory, and additional functional studies were performed if required. Pathogenic or likely pathogenic variants were detected in 6 of 22 (27%) patients. Monoallelic variants of uncertain significance were also identified in a further 4 of 22 patients (18%). Pathogenic variants, likely pathogenic variants, or variants of uncertain significance were found in TNFRSF13B, TNFRSF13C, ICOS, AICDA, IL21R, NFKB2, and CD40LG, including novel variants and variants with unexpected inheritance pattern. Targeted amplicon NGS is an effective tool to identify monogenic disease-causing variants in CVID, and is comparable or superior to other NGS methods. Moreover, targeted amplicon NGS identified patients who may benefit from targeted therapeutic strategies and had important implications for family members.
Details
- Title
- A novel targeted amplicon Next-Generation sequencing gene panel for the diagnosis of common variable immunodeficiency has a high diagnostic yield
- Authors/Creators
- W. Kermode (Author/Creator) - The University of Western AustraliaD. De Santis (Author/Creator) - The University of Western AustraliaL. Truong (Author/Creator) - Fiona Stanley HospitalE. Della Mina (Author/Creator) - Garvan Institute of Medical ResearchS. Salman (Author/Creator) - Queen Elizabeth II Medical CentreG. Thompson (Author/Creator) - Queen Elizabeth II Medical CentreD. Nolan (Author/Creator) - Royal Perth HospitalR. Loh (Author/Creator) - Princess Margaret Hospital for ChildrenD Mallon (Author/Creator) - Fiona Stanley HospitalA. McLean-Tooke (Author/Creator) - Queen Elizabeth II Medical CentreM. John (Author/Creator) - Royal Perth HospitalS.G. Tangye (Author/Creator) - Garvan Institute of Medical ResearchM. O'Sullivan (Author/Creator) - Fiona Stanley HospitalL.J. D'Orsogna (Author/Creator) - The University of Western Australia
- Publication Details
- The Journal of Molecular Diagnostics, Vol.24(6), pp.586-599
- Publisher
- Elsevier Inc. on behalf of the Association for Molecular Pathology and American Society for Investigative Pathology.
- Identifiers
- 991005542598407891
- Copyright
- © 2022 Crown Copyright.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.1437 Immunodeficiency Disorders
- Web Of Science research areas
- Pathology
- ESI research areas
- Clinical Medicine