Detection of a novel mutation in NLRP3/CIAS1 gene in an Indian child with Neonatal-Onset Multisystem Inflammatory Disease (NOMID)
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Neonatal-Onset Multisystem Inflammatory Disease (NOMID) or Chronic Infantile Neurologic Cutaneous Articular (CINCA) syndrome is a monogenic autoinflammatory disorder characterized by urticarial skin rash, fever, chronic meningitis and joint manifestations. Here we report a case of an Indian male child who presented at the age of 9 months with fever, respiratory distress, urticarial skin rash, arthritis, and neuroregression. Suspecting NOMID/CINCA syndrome, the child’s blood was sent to the Jaslok Hospital and Research Centre for mutation analysis of the CIAS1/NLRP3 gene. The DNA was screened for mutations in exon 3 of CIAS1/NLRP3 gene by automated Sanger sequencing. DNA sequencing showed a novel heterozygous c.1813A➔G, p.R605G mutation in exon 3 of CIAS1/NLRP3 gene (ref no NM_001243133.1). His parents tested negative for this mutation. We therefore identified a novel de novo mutation in this family in the CIAS1/NLRP3 gene responsible for the child’s clinical features.
Keywordsde novo mutation NLRP3/CIAS1 gene NOMID/CINCA Novel mutation
The authors thank Jaslok Hospital and Research Centre for their laboratory support.
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 2.Prieur AM (2001) A recently recognized chronic inflammatory disease of early onset characterized by the triad of rash, central nervous system involvement and arthropathy. Clin Exp Rheumatol 19:103–106Google Scholar
- 3.Aksentijevich I, Nowak M, Mallah M, Chae JJ, Watford WT, Hofmann SR, Stein L, Russo R, Goldsmith D, Dent P, Rosenberg HF, Austin F, Remmers EF, Balow JE, Rosenzweig S, Komarow H, Shoham NG, Wood G, Jones J, Mangra N, Carrero H, Adams BS, Moore TL, Schikler K, Hoffman H, Lovell DJ, Lipnick R, Barron K, O'Shea JJ, Kastner DL, Goldbach-Mansky R (2002) 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 46:3340–3348Google Scholar
- 4.Khemani C, Khubchandani R (2007) CINCA syndrome. Indian Pediatr 44:933–936Google Scholar
- 5.Simon A, Van Deer JWM, Drenth JPH (2017) Familial autoinflammatory syndromes. In Kelley and Firestein’s textbook of rheumatology, chapter 97, 10th edn, vol 2, pp 1666–1684Google Scholar
- 6.De Jesus AA, Mansky RG (2014) Classic Autoinflammatory diseases: Monogenic autoinflammatory diseases caused by defects in CIAS1, MEFV, TNFRSF1A, MVK and PSTPIP1. In Stiehm’s immune deficiencies, chapter 24, pp 517–550Google Scholar
- 7.Feldmann J, Prieur MA, Quartier P, Berquin P, Certain S, Cortis E, Teillac-Hamel D, Fischer A, de Saint BG (2002) Chronic infantile neurological cutaneous and articular syndrome id caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet 71:198–203CrossRefGoogle Scholar
- 12.Rowczenio DM, Gomes SM, Arostegui JI, Mensa-Vilaro A, Omoyinmi E, Trojer H, Baginska A, Baroja-Mazo A, Pelegrin P, Savic S, Lane T, Williams R, Brogan P, Lachmann HJ, Hawkins PN (2017) Late-onset cryopyrin-associated periodic syndromes caused by somatic NLRP3 Mosaicism–UK single centre experience. Front Immunol 8:1410–1419CrossRefGoogle Scholar