Mutation Analysis of the IL36RN Gene in 14 Japanese Patients with Generalized Pustular Psoriasis. Issue 1 (11th October 2012)

• Record Type: Journal Article
• Authors: Farooq, Muhammad; Nakai, Hiroyuki; Fujimoto, Atsushi; Fujikawa, Hiroki; Matsuyama, Asako; Kariya, Naoyuki; Aizawa, Atsuko; Fujiwara, Hiroshi; Ito, Masaaki; Shimomura, Yutaka
• Is Part Of: Human mutation. Volume 34:Issue 1(2013:Jan.)
• Page Start: 176
• Page End: 183
• Publication Date: 2012-10-11
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22203
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>Generalized pustular psoriasis (GPP) is a rare, potentially life threatening, and aggressive form of psoriasis, which is characterized by sudden onset with repeated episodic skin inflammation leading to pustule formation. Familial GPP is known to be caused by recessively inherited mutations in the <italic>IL</italic><italic>36</italic><italic>RN</italic> gene, which encodes interleukin 36 receptor antagonist (IL‐36Ra). In this article, we performed mutation analysis of the <italic>IL</italic><italic>36</italic><italic>RN</italic> gene in 14 Japanese patients with GPP, and identified mutations in two of these patients analyzed. One patient was compound heterozygous for mutations c.115+6T>C and c.368C>G (p.Thr123Arg), whereas the other carried compound heterozygous mutations c.28C>T (p.Arg10*) and c.115+6T>C in the <italic>IL</italic><italic>36</italic><italic>RN</italic> gene. Expression studies using total RNA from the patients' skin revealed that the mutation c.115+6T>C resulted in skipping of exon 3, leading to a frameshift and a premature termination codon (p.Arg10Argfs*1). The protein structure analysis suggested that the missense mutation p.Thr123Arg caused misfolding and instability of <italic>IL</italic>‐36Ra protein. <italic>In vitro</italic> studies in cultured cells showed impaired expression of the p.Thr123Arg mutant IL‐36Ra protein, which failed to antagonize the IL‐36 signaling pathway. Our data further underscore the critical role of <italic>IL</italic><italic>36</italic><italic>RN</italic> in pathogenesis of GPP.</p> </abstract>