Somatic mosaicism in adult-onset TNF receptor-associated periodic syndrome (TRAPS)

Background: Somatic mosaicism is to date an uncommon finding in genetic autoinflammatory syndromes such as Cryopyrin-associated periodic syndrome, Blau syndrome, and TNF receptor-associated periodic syndrome (TRAPS). However, somatic mosaicism may be particularly important in adult-onset or atypical phenotypes of these conditions. Herein, we report a unique adult-onset TRAPS patient presenting with intermittent daily fever for 3 weeks, rash, peritonitis, and lymphadenopathy, who was found with hematopoietic mosaicism involving different white blood cell populations. Methods: Patient's lymphocyte genomic DNA was initially analyzed by periodic fever seven-gene next-generation sequencing panel. Genomic DNAs extracted from patient's hair roots, buccal swab, and subpopulations of white blood cells were subsequently examined on the identified TNFRSF1A variant using Sanger sequencing. Results: A de novo mosaic missense variant, c.265 T>C(p.Phe89Leu), in the TNFRSF1A gene was found in the patient's buccal swab, B cells, neutrophils, and NK cells but not detected in monocytes, T cells, and hair roots. Conclusion: These data provide additional information about somatic mosaicism in autoinflammatory conditions and provide new insights regarding cellular players that are indispensable for the phenotypic expression of TRAPS.