Pityriasis Rubra Pilaris Type V as an Autoinflammatory Disease by <i>CARD14</i> Mutations

Abstract

<h3>Importance</h3> We found<i>CARD14</i>mutations (2 de novo novel mutations and another previously reported mutation) in 3 of 3 patients with pityriasis rubra pilaris (PRP) type V, but not in patients with PRP of other types. Our findings, combined with the published literature, suggest that type V PRP, both familial and sporadic, can be caused by<i>CARD14</i>mutations. Detailed clinical observation revealed that all 3 patients displayed unique patchy macular brown hyperpigmentation. <h3>Objective</h3> To further determine how often patients with PRP have pathogenic mutations in<i>CARD14</i>and to elucidate which clinical subtype of PRP is caused by<i>CARD14</i>mutations. <h3>Design, Setting, and Participants</h3> We sequenced the entire coding regions of<i>CARD14</i>in genomic DNA from patients with 5 clinical subtypes of PRP. The detailed clinical features were analyzed in all the patients. The pathogenicity of each mutation was evaluated by several computational predictions. PRP was classified into 6 subgroups, types I to VI, based on clinical criteria. We categorized all the patients with PRP into the clinical subtypes using the classic PRP classification; 22 cases of PRP with varying subtypes were studied. <h3>Main Outcomes and Measures</h3> The prevalence of<i>CARD14</i>mutations in each subtype of PRP was evaluated. Clinical features and characteristics of patients with PRP with<i>CARD14</i>mutations were analyzed. <h3>Results</h3> Overall 22 patients with PRP were included in our study (12 men, 10 women; mean [SD] age, 26 [18] years). Among 3 patients with PRP type V, all were found to have<i>CARD14</i>mutations: 2 de novo novel mutations (p.Cys127Ser and p.Gln136Leu), and another previously reported mutation (p.Gly117Ser). All were close to the reported pathogenic domains. In silico analysis of all 3 mutations suggested that they are functionally relevant to pathogenesis. All 3 patients displayed unique patchy macular brown hyperpigmentation additionally to other typical features of PRP. Patients with PRP type I and type IV, 1 patient each, had the rare variants in<i>CARD14</i>. <h3>Conclusions and Relevance</h3> Pityriasis rubra pilaris type V is a distinct variant of PRP that is caused by<i>CARD14</i>mutations. In addition, a rare variant of<i>CARD14</i>might also be implicated in the pathophysiology of other forms of PRP.