Pityriasis Rubra Pilaris Type V as an Autoinflammatory Disease by CARD14 Mutations.

TLDR: Pityriasis rubra pilaris type V is a distinct variant of PRP that is caused by CARD14 mutations, and in silico analysis of all 3 mutations suggested that they are functionally relevant to pathogenesis.

Abstract: Importance We foundCARD14mutations (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 byCARD14mutations. Detailed clinical observation revealed that all 3 patients displayed unique patchy macular brown hyperpigmentation. Objective To further determine how often patients with PRP have pathogenic mutations inCARD14and to elucidate which clinical subtype of PRP is caused byCARD14mutations. Design, Setting, and Participants We sequenced the entire coding regions ofCARD14in 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. Main Outcomes and Measures The prevalence ofCARD14mutations in each subtype of PRP was evaluated. Clinical features and characteristics of patients with PRP withCARD14mutations were analyzed. Results 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 haveCARD14mutations: 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 inCARD14. Conclusions and Relevance Pityriasis rubra pilaris type V is a distinct variant of PRP that is caused byCARD14mutations. In addition, a rare variant ofCARD14might also be implicated in the pathophysiology of other forms of PRP.