Chear, Chai Teng and Nallusamy, Revathy and Canna, Scott W. and Chan, Kwai Cheng and Baharin, Mohd Farid and Hishamshah, Munirah and Ghani, Hamidah and Ripen, Adiratna Mat and Bin Mohamad, Saharuddin (2020) A novel de novo NLRC4 mutation reinforces the likely pathogenicity of specific LRR domain mutation. CLINICAL IMMUNOLOGY, 211. ISSN 15216616, DOI https://doi.org/10.1016/j.clim.2019.108328.
Full text not available from this repository.Abstract
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.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Health, Malaysia [Grant No: NMRR-16-892-31023], National Institute of Allergy and Infectious Diseases [Grant No: K22AI123366] |
| Uncontrolled Keywords: | Autoinflammatory disease; NLRC4; Inflammasome; Whole exome sequencing |
| Subjects: | Q Science > Q Science (General) Q Science > QH Natural history > QH301 Biology |
| Divisions: | Faculty of Science > Institute of Biological Sciences |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 06 Nov 2024 04:04 |
| Last Modified: | 06 Nov 2024 04:04 |
| URI: | http://eprints.um.edu.my/id/eprint/36911 |
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