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Mutation Analysis of the IL 36 RN Gene in 14 Japanese Patients with Generalized Pustular Psoriasis
Author(s) -
Farooq Muhammad,
Nakai Hiroyuki,
Fujimoto Atsushi,
Fujikawa Hiroki,
Matsuyama Asako,
Kariya Naoyuki,
Aizawa Atsuko,
Fujiwara Hiroshi,
Ito Masaaki,
Shimomura Yutaka
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22203
Subject(s) - generalized pustular psoriasis , missense mutation , mutation , biology , exon , gene , genetics , mutant , frameshift mutation , pathogenesis , compound heterozygosity , psoriasis , microbiology and biotechnology , immunology
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 IL 36 RN gene, which encodes interleukin 36 receptor antagonist ( IL ‐36 R a). In this article, we performed mutation analysis of the IL 36 RN 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 IL 36 RN 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 IL ‐36 R a protein. In vitro studies in cultured cells showed impaired expression of the p.Thr123Arg mutant IL ‐36 R a protein, which failed to antagonize the IL ‐36 signaling pathway. Our data further underscore the critical role of IL 36 RN in pathogenesis of GPP .