A novel de novo NLRC4 mutation reinforces the likely pathogenicity of specific LRR domain mutation

A novel de novo NLRC4 mutation reinforces the likely pathogenicity of specific LRR domain mutation

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 211(2020) vom: 01. Feb., Seite 108328
1. Verfasser: Chear, Chai Teng (VerfasserIn)
Weitere Verfasser: Nallusamy, Revathy, Canna, Scott W, Chan, Kwai Cheng, Baharin, Mohd Farid, Hishamshah, Munirah, Ghani, Hamidah, Ripen, Adiratna Mat, Mohamad, Saharuddin Bin
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2020
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Case Reports Journal Article Research Support, Non-U.S. Gov't Autoinflammatory disease Inflammasome NLRC4 Whole exome sequencing CARD Signaling Adaptor Proteins CXCL9 protein, human Calcium-Binding Proteins mehr... Chemokine CXCL9 IL18 protein, human Interleukin-18 NLRC4 protein, human
Beschreibung
Zusammenfassung:Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Autoinflammatory disorders are characterized by dysregulated innate immune response, resulting in recurrent uncontrolled systemic inflammation and fever. Gain-of-function mutations in NLRC4 have been described to cause a range of autoinflammatory disorders. We report a twelve-year-old Malay girl with recurrent fever, skin erythema, and inflammatory arthritis. Whole exome sequencing and subsequent bidirectional Sanger sequencing identified a heterozygous missense mutation in NLRC4 (NM_001199138: c.1970A > T). This variant was predicted to be damaging in silico, was absent in public and local databases and occurred in a highly conserved residue in the leucine-rich repeat (LRR) domain. Cytokine analysis showed extremely high serum IL-18 and IL-18/CXCL9 ratio, consistent with other NLRC4-MAS patients. In summary, we identified the first patient with a novel de novo heterozygous NLRC4 gene mutation contributing to autoinflammatory disease in Malaysia. Our findings reinforce the likely pathogenicity of specific LRR domain mutations in NLRC4 and expand the clinical spectrum of NLRC4 mutations
Beschreibung:Date Completed 04.08.2020
Date Revised 10.02.2021
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2019.108328