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Case Reports
. 2019 Aug;7(8):e791.
doi: 10.1002/mgg3.791. Epub 2019 Jul 10.

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

Apostolos Kontzias  1 , Samaneh K Zarabi  2 , Cassandra Calabrese  3 , Yan Wang  4 , LuAnn Judis  5 , QingPing Yao  1 , Yu-Wei Cheng  4   5
Affiliations
Case Reports

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

Apostolos Kontzias et al. Mol Genet Genomic Med. 2019 Aug.

Abstract

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.

Keywords: TRAPS; autoinflammatory; mosaicism.

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Conflict of interest statement

AK has received consultant fees and honorariums from Novartis and Horizon

Figures

Figure 1
Figure 1
(a) Sanger sequencing of the TNFRSF1A exon 3 shows the variant allele C, instead of the wild‐type allele T, in the patient's blood and buccal swab. No variant was identified in the wild‐type control blood and the patient hair root. (b) Sanger sequencing of the TNFRSF1A exon 3 in the white blood cells displays the variant allele in the B cells, NK cells, and neutrophils. With an estimated variant allele fraction at 25%–45% by measuring the fluorescence peak heights between the wild‐type and the variant alleles. There was no variant identified in the monocyte and T cell subpopulations
See this image and copyright information in PMC

References

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