title: Phenotype-genotype analysis of cryopyrin-associated periodic syndromes (CAPS): description of a rare non-exon 3 and a novel CIAS1 missense mutation.
abstract: We describe in this paper the phenotype-genotype analysis of a Brazilian cohort of patients with cryopyrin-associated periodic syndromes (CAPS). Patient 1 presented with an urticarial rash and recurrent fever exacerbated by cold weather, arthritis, and anterior uveitis, thus, receiving a clinical diagnosis of familial cold autoinflammatory syndrome. CIAS1 sequencing identified the T436I mutation, previously associated to a clinical phenotype of chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease. Patient 2 developed a papular exanthema with daily fever shortly after birth, frontal bossing, patellae enlargement, and cognitive and motor impairments. Sequencing identified the exceedingly rare G755R CIAS1 mutation in exon 4. Patient 3 developed skin rash and articular symptoms 6 h after birth, followed by aseptic meningitis. He was found to have the novel C148Y missense mutation in CIAS1. This report expands the spectrum of CIAS1 mutations associated to clinical disease, suggests that the same mutation can be associated with different clinical syndromes, and supports the evidence that CAPS patients should always be screened for mutations outside exon 3.
authors: Pediatric Rheumatology Unit, University of São Paulo, São Paulo, Brazil.
authors: Adriana A
authors: AA
authors: Jesus
authors: Clovis A
authors: CA
authors: Silva
authors: Gesmar R
authors: GR
authors: Segundo
authors: Ivona
authors: I
authors: Aksentijevich
authors: Erika
authors: E
authors: Fujihira
authors: Mônica
authors: M
authors: Watanabe
authors: Magda
authors: M
authors: Carneiro-Sampaio
authors: Alberto J S
authors: AJ
authors: Duarte
authors: João B
authors: JB
authors: Oliveira
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005091:Exons / Q000235:genetics; D019066:Facies; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010641:Phenotype; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human