title: De novo 19q13.42 duplications involving NLRP gene cluster in a patient with systemic-onset juvenile idiopathic arthritis.
abstract: Systemic-onset juvenile idiopathic arthritis (s-JIA) is a rare inflammatory disease classified as a subtype of chronic childhood arthritis, manifested by spiking fever, erythematous skin rash, pericarditis and hepatosplenomegaly. The genetic background underlying s-JIA remains poorly understood. To detect disease-related copy number variations (CNVs), we performed single-nucleotide polymorphism array analysis in 50 patients with s-JIA. We detected many CNVs, but most of them were inherited from either of normal-phenotype parents. However, in one patient, we could identify two de novo microduplications at 19q13.42 with the size of 77 and 622 kb, separated by a 109-kb segment of normal copy number. The duplications encompass NLRP family (NLRP2, NLRP9 and NLRP11) as well as IL11 and HSPBP1, all of which have an important role in inflammatory pathways. These genes may significantly contribute to the pathogenesis of s-JIA.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tadaki
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.forename: Akira
authors.initials: A
authors.lastname: Nishimura-Tadaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Imagawa
authors.forename: Masako
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Ryoki
authors.initials: R
authors.lastname: Hara
authors.forename: Utako
authors.initials: U
authors.lastname: Kaneko
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kishi
authors.forename: Takako
authors.initials: T
authors.lastname: Miyamae
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Doi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: Haruya
authors.initials: H
authors.lastname: Sakai
authors.forename: Shumpei
authors.initials: S
authors.lastname: Yokota
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D001171:Arthritis, Juvenile / Q000235:genetics*; D058674:Chromosome Duplication / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D005810:Multigene Family / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D048868:Adaptor Proteins, Signal Transducing