DITRA via the IL36RN Gene

Deficiency of Interleukin 36 Receptor Antagonist Deficiency (DITRA) is an autoinflammatory disease with patients developing recurrent erythematous rashes and fevers with onset typically occurring between birth and 10 years of age. Secondary skin infections, diarrhea, dysphagia, asthenia and failure to thrive have also been reported (Sanchez et al. 2013; Marrakchi et al. 2011). Genetic testing is helpful in the differential diagnosis of DITRA from other psoriasis conditions including CARD14 mediated psoriasis (CAMPS) as well as other periodic fever syndromes. Treatment for patients with DITRA includes IL1 receptor antagonists such as anakinra and IL17 inhibition (Rossi-Semerano et. al. 2013; Sanchez et al. 2013).

DITRA is inherited in an autosomal recessive manner through pathogenic variants in the IL36RN gene. The majority of pathogenic variants to date are missense and occur throughout the coding region. Small deletions, splice site, and nonsense changes have also been reported (Farooq et al. 2013; Hussain et al. 2015). A p.Leu27Pro change has been reported as a founder variant found within Tunisian populations (Marrakchi et al. 2011). The IL36RN gene encodes the interleukin 36 receptor antagonist and is responsible for regulating inflammatory responses. Missense changes, such as p.Leu27Pro, have been shown to result in unregulated secretion of proinflammatory cytokines such as IL8 in keratinocytes leading to pustular psoriasis (Marrakchi et al. 2011).

Clinical sensitivity cannot be estimated because only a small number of cases have been reported to date. Analytical sensitivity should be high as all pathogenic variants reported to date are detectable by sequencing.

This test provides full coverage of all coding exons of the IL36RN gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).