A novel mutation in IL36RN underpins childhood pustular dermatosis
نویسندگان
چکیده
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.
منابع مشابه
Generalized pustular psoriasis in infant with heterozygous mutation in the IL36RN gene successfully treated with infliximab
Introduction Homozygous missense mutation in the IL36RN gene resulting in deficiency of interleukin-36-receptor antagonist (DITRA) is phenotypically presented as severe generalized pustular psoriasis starting in early childhood. Compound heterozygous cases have been described with the same DITRA phenotype, but to our knowledge heterozygous IL36RN mutation related to severe generalized pustular ...
متن کاملHomozygous missense mutation in IL36RN in generalized pustular dermatosis with intraoral involvement compatible with both AGEP and generalized pustular psoriasis.
Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Sanlorenzo, Vujic, Cleaver, Ortiz-Urda. Critical revision of the manuscript for important intellectual content: Sanlorenzo, Vujic, Posch, Quaglino, Ortiz-Urda. Statistical analysis: Sanlorenzo. Obtained funding: Ortiz-Urda. Administrative, technical, or material support: Vujic, Cleaver, Ortiz-Urda. Study ...
متن کاملOR6-006 – IL36RN alleles in skin auto-inflammation
Results We found IL36RN recessive mutations in patients with GPP (7/84) and localised pustular psoriasis (2/9 cases of Acrodermatitis Continua of Hallopeau and 3/139 cases of plamar-plantar pustulosis), but not among PV cases. Of note, we also identified several affected individuals who carried a single heterozygous mutation. In fact, we uncovered a significant enrichment of heterozygous IL36RN...
متن کاملP02-002 - IL36RN mutations in patients with DITRA
Introduction Loss-of-function mutations in the IL36RN gene define a novel recessively inherited autoinflammatory syndrome named deficiency of IL-36 receptor antagonist (DITRA). This genetically determined deficiency was first described in a subgroup of patients with generalized pustular psoriasis. It is a life-threatening condition characterized by recurrent episodes of severe skin inflammation...
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