Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome
- PMID: 16255047
- DOI: 10.1002/art.21404
Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome
Abstract
Chronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) is a severe inflammatory disease that was recently found to be associated with mutations in CIAS1. However, CIAS1 mutations have been detected in only half of CINCA syndrome patients, and it remains unclear which genes are responsible for the syndrome in the remaining patients. We describe here a patient with CINCA syndrome who exhibited CIAS1 somatic mosaicism. We genetically analyzed the CIAS1 gene in various blood cells and the buccal mucosa of the patient. The production of interleukin-1beta (IL-1beta) by peripheral blood mononuclear cells (PBMCs) was measured by enzyme-linked immunosorbent assay, and the ability of the mutant CIAS1 gene to enhance ASC-dependent NF-kappaB activation was assessed to confirm that the mutations of CIAS1 found were responsible for the patient's clinical manifestations of the CINCA syndrome. The patient had 1 heterologous single-nucleotide polymorphism, 587G>A (S196N), and 1 heterologous mutation, 1709A>G (Y570C), in exon 3 of CIAS1. The latter mutation was found to occur as somatic mosaicism. The patient's PBMCs produced a large amount of IL-1beta in the absence of stimulation, unlike those from controls or from his mother, who also bore the S196N polymorphism. In addition, the Y570C mutation (with or without the S196N polymorphism) increased the ability of CIAS1 to induce ASC-dependent NF-kappaB activation, unlike the wild-type gene or the gene bearing the S196N polymorphism alone. The findings in this patient indicate that somatic mosaicism is one reason CIAS1 mutations have not been detected in some patients with CINCA syndrome.
Comment in
-
Mutational analysis in neonatal-onset multisystem inflammatory disease: comment on the articles by Frenkel et al and Saito et al.Arthritis Rheum. 2006 Aug;54(8):2703-4; author reply 2704-5. doi: 10.1002/art.22022. Arthritis Rheum. 2006. PMID: 16871551 No abstract available.
Similar articles
-
De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases.Arthritis Rheum. 2002 Dec;46(12):3340-8. doi: 10.1002/art.10688. Arthritis Rheum. 2002. PMID: 12483741 Free PMC article.
-
A somatic NLRP3 mutation as a cause of a sporadic case of chronic infantile neurologic, cutaneous, articular syndrome/neonatal-onset multisystem inflammatory disease: Novel evidence of the role of low-level mosaicism as the pathophysiologic mechanism underlying mendelian inherited diseases.Arthritis Rheum. 2010 Apr;62(4):1158-66. doi: 10.1002/art.27342. Arthritis Rheum. 2010. PMID: 20131270
-
Pattern of interleukin-1beta secretion in response to lipopolysaccharide and ATP before and after interleukin-1 blockade in patients with CIAS1 mutations.Arthritis Rheum. 2007 Sep;56(9):3138-48. doi: 10.1002/art.22842. Arthritis Rheum. 2007. PMID: 17763411
-
Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome: a review.Orphanet J Rare Dis. 2016 Dec 7;11(1):167. doi: 10.1186/s13023-016-0542-8. Orphanet J Rare Dis. 2016. PMID: 27927236 Free PMC article. Review.
-
Cryopyrinopathies: update on pathogenesis and treatment.Nat Clin Pract Rheumatol. 2008 Sep;4(9):481-9. doi: 10.1038/ncprheum0874. Epub 2008 Jul 29. Nat Clin Pract Rheumatol. 2008. PMID: 18665151 Review.
Cited by
-
Impaired cytokine responses in patients with cryopyrin-associated periodic syndrome (CAPS).Clin Exp Immunol. 2014 Sep;177(3):720-31. doi: 10.1111/cei.12361. Clin Exp Immunol. 2014. PMID: 24773462 Free PMC article.
-
[Genetics of cryopyrin-associated periodic syndrome].Z Rheumatol. 2017 May;76(4):313-321. doi: 10.1007/s00393-017-0271-y. Z Rheumatol. 2017. PMID: 28197772 Review. German.
-
Induced Pluripotent Stem Cell-Derived Monocytes/Macrophages in Autoinflammatory Diseases.Front Immunol. 2022 May 6;13:870535. doi: 10.3389/fimmu.2022.870535. eCollection 2022. Front Immunol. 2022. PMID: 35603217 Free PMC article. Review.
-
Diagnosis and Management of the Cryopyrin-Associated Periodic Syndromes (CAPS): What Do We Know Today?J Clin Med. 2021 Jan 1;10(1):128. doi: 10.3390/jcm10010128. J Clin Med. 2021. PMID: 33401496 Free PMC article. Review.
-
Novel mutation in the NRLP3 manifesting as an intermediate phenotype of cryopyrinopathies.Rheumatol Int. 2021 Jan;41(1):219-225. doi: 10.1007/s00296-020-04683-5. Epub 2020 Aug 19. Rheumatol Int. 2021. PMID: 32813153 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous