The Rapidly Expanding Genetic Spectrum of Common Variable Immunodeficiency-Like Disorders

Ameratunga, R; Edwards, ESJ; Lehnert, K; Leung, E; Woon, ST; Lea, E; Allan, C; Chan, L; Steele, R; Longhurst, H; Bryant, VL

Author(s): Ameratunga, R; Edwards, ESJ; Lehnert, K; Leung, E; Woon, ST; Lea, E; Allan, C; Chan, L; Steele, R; Longhurst, H; Bryant, VL;
Details: Publication Year 2023-02-14,Volume 11,Issue #6,Page 1646-1664
Journal Title: Journal of Allergy and Clinical Immunology In Practice
Abstract: The understanding of common variable immunodeficiency disorders (CVID) is in evolution. CVID was previously a diagnosis of exclusion. New diagnostic criteria have allowed the disorder to be identified with greater precision. With the advent of next-generation sequencing (NGS), it has become apparent that an increasing number of patients with a CVID phenotype have a causative genetic variant. If a pathogenic variant is identified, these patients are removed from the overarching diagnosis of CVID and are deemed to have a CVID-like disorder. In populations where consanguinity is more prevalent, the majority of patients with severe primary hypogammaglobulinemia will have an underlying inborn error of immunity, usually an early-onset autosomal recessive disorder. In nonconsanguineous societies, pathogenic variants are identified in approximately 20% to 30% of patients. These are often autosomal dominant mutations with variable penetrance and expressivity. To add to the complexity of CVID and CVID-like disorders, some genetic variants such as those in TNFSF13B (transmembrane activator calcium modulator cyclophilin ligand interactor) predispose to, or enhance, disease severity. These variants are not causative but can have epistatic (synergistic) interactions with more deleterious mutations to worsen disease severity. This review is a description of the current understanding of genes associated with CVID and CVID-like disorders. This information will assist clinicians in interpreting NGS reports when investigating the genetic basis of disease in patients with a CVID phenotype.
Publisher: Elsevier
Keywords: Cvid; CVID-like disorders; Digenic disorders; Epistasis; Genetics; Hypogammaglobulinemia; Inborn errors of immunity; Locid; Late-onset combined immunodeficiency; Primary immunodeficiency disorders
Research Division(s): Immunology
PubMed ID: 36796510
Publisher's Version: https://doi.org/10.1016/j.jaip.2023.01.048
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-12-13 10:19:53

Last Modified: 2023-12-13 10:23:31