title: Microarray and whole-exome sequencing analysis of familial Behçet's disease patients.
abstract: Behçet's disease (BD), a chronic systemic inflammatory disorder, is characterized by recurrent oral and genital mucous ulcers, uveitis, and skin lesions. We performed DNA microarray analysis of peripheral blood mononuclear cell (PBMC) mRNA from 41 Japanese BD patients and revealed elevated levels of interleukin (IL) 23 receptor (IL23R) mRNA in many BD patients. DNA sequencing around a SNV (Rs12119179) tightly linked to BD revealed an elevated frequency of the C genotype, consistent with a previous report that IL23R is a susceptibility locus for BD. Notably, four of these BD patients are members of familial BD; a whole-exome sequencing (WES) of these BD patients identified 19 novel single-nucleotide variations (SNVs) specific to these patients. They include heterozygous SNVs in the genes encoding IL-1 receptor-associated kinase 4 (IRAK4), nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 14 (NRP14) and melanoma antigen-encoding gene E2 (MAGEE2); IRAK4 harbors a missense mutation, whereas NRP14 and MAGEE2 harbor nonsense mutations. These SNVs may serve as genetic markers that characterize BD.
authors.affiliation: DNA-chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.|Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okuzaki
authors.affiliation: Department of Organic Fine Chemicals, The Institute of Scientific and Industrial Research, Osaka University, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan.|Department of Clinical Application of Biologics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yoshizaki
authors.affiliation: Department of Clinical Application of Biologics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kohshiro
authors.initials: K
authors.lastname: Fukushima
authors.affiliation: Riken Genesis, Co. Ltd., Riken Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Washio
authors.affiliation: DNA-chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.|Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nojima
mesh_terms: D001528:Behcet Syndrome / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D059472:Exome; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics
chemical_list: C515500:IL23R protein, human; D012333:RNA, Messenger; D018123:Receptors, Interleukin