Details

Autor(en) / Beteiligte

• de Koning, Heleen D., MD
• van Gijn, Mariëlle E., MD, PhD
• Stoffels, Monique, PhD
• Jongekrijg, Johanna, BSc
• Zeeuwen, Patrick L.J.M., PhD
• Elferink, Martin G., PhD
• Nijman, Isaac J., PhD
• Jansen, Patrick A.M., PhD
• Neveling, Kornelia, PhD
• van der Meer, Jos W.M., MD, PhD
• Schalkwijk, Joost, PhD
• Simon, Anna, MD, PhD

Titel

Myeloid lineage–restricted somatic mosaicism of NLRP3 mutations in patients with variant Schnitzler syndrome

Ist Teil von

• Journal of allergy and clinical immunology, 2015-02, Vol.135 (2), p.561-564.e4

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• No NLRP3 genetic variants were found in any of the analyzed cell types derived from 2 patients with Schnitzler syndrome without NLRP3 variants in whole blood (Table I). Because we have previously demonstrated that IL-1β is a pivotal mediator of the clinical signs of Schnitzler syndrome,2,5 we proceeded to investigate the functional consequences of the NLRP3 mosaic mutations on IL-1β and IL-6 production in PBMCs (see the Methods section in this article's Online Repository at www.jacionline.org). The identified variant is considered a benign polymorphism.E5 In patient 7 we detected a known missense mutation in the NACHT domain of the NLRP3 gene (c.1569C>G; p.F523L), which was previously reported as disease causing in 2 infants with NOMID/CINCA, a severe early-onset form of CAPS.E6Canonical SS, Variants located in a canonical splice site; Coding+SS, all variants located either in exonic regions or canonical splice sites; Indels, Insertions or deletions; Known variant (HGMD), variants described as pathogenic in the Human Gene Mutation Database (www.hgmd.org); Missense (phyloP >2.5),E4 highly conserved missense variants with a phyloP >2.5; Nonsense, nonsense variants; Nonsynonymous, variants leading to an amino acid change; Not seen before (in house), variants that have not been detected in 672 in-house sequenced whole exomes; Patient, patient who has undergone whole-exome sequencing; Total no. of variants, all variants detected by using whole-exome sequencing.