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Pityriasis Rubra Pilaris Type V as an Autoinflammatory Disease by CARD14 Mutations
Takuya Takeichi1, Kazumitsu Sugiura2, Toshifumi Nomura3
1Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan2St John's Institute of Dermatology, King's College London, Guy's Hospital, London, England.
Importance:
We found CARD14 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 CARD14 mutations. 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 in CARD14 and to elucidate which clinical subtype of PRP is caused by CARD14 mutations.
Design, Setting, And Participants:
We sequenced the entire coding regions of CARD14 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.
Main Outcomes And Measures:
The prevalence of CARD14 mutations in each subtype of PRP was evaluated. Clinical features and characteristics of patients with PRP with CARD14 mutations 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 have CARD14 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 CARD14.
Conclusions And Relevance:
Pityriasis rubra pilaris type V is a distinct variant of PRP that is caused by CARD14 mutations. In addition, a rare variant of CARD14 might also be implicated in the pathophysiology of other forms of PRP.
Insights
CARD14 mutations are the cause of pityriasis rubra pilaris (PRP) type V. These genetic alterations may also contribute to other PRP subtypes, highlighting CARD14
Area of Science:
- Genetics
- Dermatology
- Molecular Biology
Background:
- Pityriasis rubra pilaris (PRP) is a rare chronic skin disorder with six clinical subtypes.
- The genetic underpinnings of most PRP subtypes remain largely unknown.
- Investigating genetic mutations associated with specific PRP variants is crucial for understanding disease mechanisms.
Observation:
- CARD14 mutations were identified in all three studied patients with Pityriasis rubra pilaris type V.
- These mutations included two novel de novo mutations and one previously reported mutation.
- All affected patients exhibited characteristic patchy macular brown hyperpigmentation.
Findings:
- CARD14 mutations were exclusively found in Pityriasis rubra pilaris type V patients.
- In silico analysis confirmed the pathogenic potential of the identified CARD14 mutations.
- Rare CARD14 variants were also observed in patients with Pityriasis rubra pilaris types I and IV.
Implications:
- CARD14 mutations are a significant cause of Pityriasis rubra pilaris type V, encompassing both familial and sporadic cases.
- The findings suggest CARD14's role in the pathophysiology of other PRP subtypes.
- This research advances the understanding of PRP etiology and may inform future diagnostic and therapeutic strategies.
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