IL36RN – pustulosis palmaris et plantaris

Rare heterozygous IL36RN variants have been reported in cohorts of patients with palmoplantar pustulosis (PPP). In a Japanese series of 88 PPP patients, four carried single‐allele missense substitutions (c.368C>T (p.Thr123Met), p.Pro82Leu, p.Asn47Ser) without altered IL-36Ra immunohistochemical expression, yielding no significant genotype–phenotype correlation (PMID:27542682). A Han Chinese study of 51 PPP patients identified nine heterozygous substitutions (c.140A>G (p.Asn47Ser) in five, c.258G>A (p.Met86Ile) in two, c.115+6T>C, c.169G>A (p.Val57Ile)) with no impact on disease severity or onset age (p>0.1) (PMID:31789248). No familial segregation data are available, and statistical enrichment against controls was not demonstrated.

Functional assays distinguish null and hypomorphic IL36RN alleles: mutations such as p.Thr123Met show partial reduction of IL-36Ra activity in NF-κB reporter assays, whereas null alleles abrogate antagonism entirely. Hypomorphic variants are associated with both localized and generalized pustular phenotypes, but no assay has confirmed a definitive causal role in isolated PPP (PMID:27220475). Taken together, IL36RN mutations exhibit incomplete penetrance and limited genetic and experimental support in PPP.

Key Take-home: Sparse heterozygous IL36RN variants occur in PPP but lack robust enrichment, segregation or functional specificity, supporting a limited association.

References

• The Journal of dermatology • 2017 • Mutation analysis of IL36RN gene in Japanese patients with palmoplantar pustulosis. PMID:27542682
• Anais brasileiros de dermatologia • 2019 • Lack of association between mutation in IL36RN and palmoplantar pustular psoriasis in Chinese patients. PMID:31789248
• The Journal of investigative dermatology • 2016 • IL36RN Mutations Affect Protein Expression and Function: A Basis for Genotype-Phenotype Correlation in Pustular Diseases PMID:27220475

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