title: A novel mutation in IL36RN underpins childhood pustular dermatosis.
abstract: BACKGROUND
  Chronic pustular dermatoses are severe and debilitating autoinflammatory conditions that can have a monogenic basis. Their clinical features are, however, complex with considerable overlap. Null and missense mutations in the genes encoding interleukin (IL)-1 family (IL-1 and IL-36) anti-inflammatory receptor antagonist (Ra) cytokines can underlie the development of severe pustular dermatoses.
  
  
  OBJECTIVE
  We present a clinical and genetic study of four children of Pakistani descent with similar clinical presentations and treatment course, each of whom suffers from a severe pustular dermatosis, initially described as a pustular variant of psoriasis. We use DNA sequencing to refine the diagnosis of two of the children studied.
  
  
  METHODS
  Bidirectional Sanger sequencing was performed on the coding regions of the IL-1Ra and IL-36Ra genes (IL1RN and IL36RN, respectively), for the four affected children and their parents.
  
  
  RESULTS
  We identified a novel homozygous missense mutation in IL36RN in two siblings, and showed the molecular basis of the condition to be both distinct from psoriasis and distinct between the two families studied.
  
  
  CONCLUSIONS
  We describe a novel mutation which underpins the diagnosis of childhood pustular dermatosis. Molecular diagnostics can be used to aid the clinical diagnosis and potential treatment of autoinflammatory conditions.
authors: Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors: J M
authors: JM
authors: Ellingford
authors: Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors: G C M
authors: GC
authors: Black
authors: The Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
authors: T H
authors: TH
authors: Clayton
authors: The Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
authors: M
authors: M
authors: Judge
authors: The Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
authors: C E M
authors: CE
authors: Griffiths
authors: The Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
authors: R B
authors: RB
authors: Warren
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D035781:Siblings; D012871:Skin Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C122187:IL36RN protein, human; D007378:Interleukins; D017472:Receptors, Interleukin-1; D004247:DNA