Mutations in IL36RN are associated with geographic tongue

被引：36

作者：

Liang, Jianying ^{[1
]}

Huang, Peichen ^{[1
]}

Li, Huaguo ^{[1
]}

Zhang, Jia ^{[1
]}

Ni, Cheng ^{[1
]}

Wang, Yirong ^{[1
]}

Shen, Jinwen ^{[1
]}

Li, Chunxiao ^{[1
]}

Kang, Lu ^{[2
]}

Chen, Jie ^{[2
]}

Zhang, Hui ^{[1
]}

Wang, Zhen ^{[1
]}

Zhang, Zhen ^{[1
]}

Li, Ming ^{[1
]}

Yao, Zhirong ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Dermatol, Sch Med, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China

[2] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Stomatol, Sch Med, Shanghai, Peoples R China

来源：

HUMAN GENETICS | 2017年 / 136卷 / 02期

关键词：

GENERALIZED PUSTULAR PSORIASIS; BENIGN MIGRATORY GLOSSITIS; CHINESE PATIENTS; ORAL LESIONS; ANTAGONIST; EXPRESSION; VULGARIS; GENE; SKIN; INTERLEUKIN-36;

D O I：

10.1007/s00439-016-1750-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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-36 gamma 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-36 gamma proteins in tongue tissue.

引用

页码：241 / 252

页数：12

共 27 条

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