title: Mutations in IL36RN are associated with geographic tongue.
abstract: 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.
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Peichen
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Huaguo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ni
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Yirong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Stomatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Stomatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. aypyslm@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. dermatology.yao@sohu.com.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000293:Adolescent; D002648:Child; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D060005:Genotyping Techniques; D005929:Glossitis, Benign Migratory / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D011487:Protein Conformation; D011565:Psoriasis / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D014059:Tongue / Q000378:metabolism; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; C508589:IL36G protein, human; C122187:IL36RN protein, human; D007375:Interleukin-1; D007378:Interleukins