Autoinflammatory Diseases: Germline vs. Somatic Mosaic Variations
Résumé
During the period of 2018-2023, we have identified 10 pathogenic variations in the NLRP3 gene (Figure 1) including:-8 different mosaic variations in 11 independent patients-2 different germline variations in 3 independent patients. A total of 34 mosaic and 88 germline NLRP3 variations have been reported in the literature to date (Figure 1). Clinically, NLRP3 mosaic variations are associated with various NLRP3-AID phenotypes ranging from late-onset urticaria in the context of MWS to CINCA. Conclusions This study emphasizes the high frequency of somatic mosaic variations in NLRP3-AIDs. The phenotypic spectrum of NLRP3-AIDs appears to be related to both the germinal/mosaic status and the localization in cryopyrin of the underlying variations. Mosaic variations in the NLRP3, TNFRSF1A, and NLRC4 genes can cause symptoms even when present at very low allele frequencies (below 5%). Furthermore, misdiagnosis may occur due to the low allele frequency of mosaic variations.
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