Gene Mutation Analysis in a Korean Patient with Early-Onset and Recalcitrant Generalized Pustular Psoriasis

Song, Hyo Sang; Yun, Su Jin; Park, Sun; Lee, Eun‐So

doi:10.5021/ad.2014.26.3.424

Cited by 10 publications

(8 citation statements)

References 5 publications

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“…Sugiura et al (2013) also revealed the same result and suggested that p.Arg10ArgfsX1(c.115+6T>C) is one of the founder mutations for GPP in the Japanese population. Furthermore, p.Arg10ArgfsX1(c.115+6T>C) was reported in Chinese (Li et al 2013, 2014), Korean (Song et al 2014) and Malay (Setta-Kaffetzi et al 2013) patients with GPP in homozygous/compound heterozygous, or heterozygous state. In current study, by three-dimensional conformation analysis, the mutation could lead to a truncated protein and lose the functional domain.…”

Section: Discussionmentioning

confidence: 94%

Mutations in IL36RN are associated with geographic tongue

Liang

Huang

et al. 2016

Hum Genet

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Geographic tongue (GT) is a benign inflammatory disorder of unknown etiology. Epidemiology and histopathology in previous studies found that generalized pustular psoriasis (GPP) is a factor associated with GT, but the molecular mechanism remains obscure. To investigate the mechanism of GT, with and without GPP, three cohorts were recruited to conduct genotyping of IL36RN, which is the causative gene of GPP. In a family spanning three generations and diagnosed with only GT (“GT alone”), GT was caused by the c.115+6T>C/p.Arg10ArgfsX1 mutation in the IL36RN gene. An autosomal dominant inheritance pattern with incomplete penetrance was observed. In the cohort consisting of sporadic cases of “GT alone” (n = 48), significant associations between GT and three IL36RN variants (c.115+6T>C/p.Arg10ArgfsX1, c.169G>A/p.Val57Ile and c.29G>A/p.Arg10Gln) were shown. In the GPP patient cohort (n = 56) and GPP family member cohort (n = 67), a significant association between the c.115+6T>C mutation and the simultaneous presence of GPP and GT was observed when compared to the presence of GPP without GT (P < 0.05). Biopsies revealed similarities among GT patients with different genotypes (AA, Aa and aa), with the neutrophils prominently infiltrating the epidermis. Western-blot analysis showed that the expression ratio of IL-36Ra/IL-36γ in lesioned tongues with individuals harboring different genotypes (AA, Aa and aa, n = 3, respectively) decreased significantly compared to controls (n = 3). We describe the mechanism of GT for the first time: some cases of GT are caused by IL36RN mutations, while those lacking mutations are associated with an imbalance in expression between IL-36Ra and IL-36γ proteins in tongue tissue.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-016-1750-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 94%

Mutations in IL36RN are associated with geographic tongue

Liang

Huang

et al. 2016

Hum Genet

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“…Recent treatment of juvenile DITRA (C115+6T>C/p.Arg10ArgfsX1) with tumor necrosis factor-α blockers (infliximab) was reported to be successful 8 and unsuccessful. 9 Similar treatments in patients with identical mutations result in different outcomes, illustrating the complexity of the disease and its treatment. A recent publication showed a possible correlation between disease severity in DITRA, mutation of the IL36RN gene, and IL36RN protein expression.…”

Section: Discussionmentioning

confidence: 99%

Juvenile interleukin-36 receptor antagonist deficiency (DITRA) with c.80T>C (p.Leu27Pro) mutation successfully treated with etanercept and acitretin

et al. 2018

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“…IL-36 is overexpressed in psoriatic lesional skin 12 20 . On the other hand, mutations of the gene for IL-36Ra were reported in patients with intractable and severe GPP 14 15 17 . Studies of IL-36 and its antagonist in patients with AGEP have also been reported 16 .…”

Section: Discussionmentioning

confidence: 99%

“…However, comparative immunohistochemical studies between GPP and AGEP are relatively few 7 . Mutations of the gene for IL-36 receptor antagonist (IL-36Ra) were recently reported in patients with GPP and AGEP 14 15 16 17 . Such findings support the idea that a common pathomechanism might exist in the two diseases.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Comparison of IL-36 and the IL-23/Th17 Axis of Generalized Pustular Psoriasis and Acute Generalized Exanthematous Pustulosis

et al. 2016

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BackgroundCutaneous pustular disorders include generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP).ObjectiveTo identify differences between GPP and AGEP, here we immunohistochemically evaluated interleukin (IL)-36 and the IL-23/Th17 axis.MethodsThis retrospective comparative immunohistochemical study was completed using 11 biopsies of 11 cases of GPP and 11 biopsies of 11 cases of AGEP. Through staining with the anti-IL-36-alpha (IL-36α), anti-IL-36 receptor antagonist (IL-36Ra), anti-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), anti-IL-23, anti-IL-17, and anti-IL-8 antibodies, main expression location and intensity were visualized in the epidermis and dermis.ResultsIn both diseases, diffuse IL-36α expression was observed in the epidermis. IL-36Ra expression was observed in the dermal perivascular area as well as in the epidermis. NF-κB expression was observed in the epidermis and perivascular dermal area. Diffuse IL-23 and IL-17 expression was seen in the whole epidermis and the perivascular dermal area. IL-8 was expressed in the subcorneal pustules and parakeratotic area. Contrary to other cytokines, IL-23 expression in the epidermis of patients with GPP was more intense than only that in patients with AGEP.ConclusionCommon pathomechanisms might exist in the development of GPP and AGEP based on these immunohistochemical results, but further studies are needed.

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Gene Mutation Analysis in a Korean Patient with Early-Onset and Recalcitrant Generalized Pustular Psoriasis

Cited by 10 publications

References 5 publications

Mutations in IL36RN are associated with geographic tongue

Mutations in IL36RN are associated with geographic tongue

Juvenile interleukin-36 receptor antagonist deficiency (DITRA) with c.80T>C (p.Leu27Pro) mutation successfully treated with etanercept and acitretin

Immunohistochemical Comparison of IL-36 and the IL-23/Th17 Axis of Generalized Pustular Psoriasis and Acute Generalized Exanthematous Pustulosis

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