Somatic mutations in autoinflammatory and autoimmune disease.

Autor: Torreggiani S; Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. sofia.torreggiani@nih.gov.; Epidemiology and Human Genetics, Graduate Program in Life Sciences, University of Maryland School of Medicine, Baltimore, MD, USA. sofia.torreggiani@nih.gov., Castellan FS; Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, NY, USA., Aksentijevich I; Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Beck DB; Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, NY, USA. David.Beck@nyulangone.org.
Jazyk: angličtina
Zdroj: Nature reviews. Rheumatology [Nat Rev Rheumatol] 2024 Nov; Vol. 20 (11), pp. 683-698. Date of Electronic Publication: 2024 Oct 11.
DOI: 10.1038/s41584-024-01168-8
Abstrakt: Somatic mutations (also known as acquired mutations) are emerging as common, age-related processes that occur in all cells throughout the body. Somatic mutations are canonically linked to malignant processes but over the past decade have been increasingly causally connected to benign diseases including rheumatic conditions. Here we outline the contribution of somatic mutations to complex and monogenic immunological diseases with a detailed review of unique aspects associated with such causes. Somatic mutations can cause early- or late-onset rheumatic monogenic diseases but also contribute to the pathogenesis of complex inflammatory and immune-mediated diseases, affect disease progression and define new clinical subtypes. Although even variants with a low variant allele fraction can be pathogenic, clonal dynamics could lead to changes over time in the proportion of mutant cells, with possible phenotypic consequences for the individual. Thus, somatic mutagenesis and clonal expansion have relevant implications in genetic testing and counselling. On the basis of both increased recognition of somatic diseases in clinical practice and improved technical and bioinformatic processes, we hypothesize that there will be an ever-expanding list of somatic mutations in various genes leading to inflammatory conditions, particularly in late-onset disease.
(© 2024. Flore S. Castellan and David B. Beck. Parts of this work were authored by US Federal Government authors and are not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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