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: Daisuke Okuzaki, Kazuyuki Yoshizaki, Toshio Tanaka, Toru Hirano, Kohshiro Fukushima, Takanori Washio, Hiroshi Nojima
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 19456 (Jan 20 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26785681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL23R protein, human
• RNA, Messenger
• Receptors, Interleukin

Topics

• Behcet Syndrome (genetics)
• Case-Control Studies
• Cluster Analysis
• Exome
• Female
• Gene Expression
• Gene Expression Profiling
• Genetic Loci
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Genotype
• High-Throughput Nucleotide Sequencing
• Humans
• Leukocytes, Mononuclear (metabolism)
• Male
• Oligonucleotide Array Sequence Analysis
• Polymorphism, Single Nucleotide
• RNA, Messenger (genetics)
• Receptors, Interleukin (genetics)