title: Pityriasis Rubra Pilaris Type V as an Autoinflammatory Disease by CARD14 Mutations.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan2St John's Institute of Dermatology, King's College London, Guy's Hospital, London, England.
authors.forename: Takuya
authors.initials: T
authors.lastname: Takeichi
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Sugiura
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Sakamoto Clinic, Fujieda, Japan.
authors.forename: Taiko
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Faculty of Medicine, Department of Dermatology, Kinki University, Osaka-Sayama, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Oiso
authors.affiliation: Division of Dermatology, Ogikubo Hospital, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Futei
authors.affiliation: Department of Dermatology, Fujisaki Hospital, Saga, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Fujisaki
authors.affiliation: Joy Dermatological Clinic, Yamaguchi, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Koizumi
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan10Department of Dermatology, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Dermatology, Faculty of Medicine, Oita University, Yufu, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hatano
authors.affiliation: Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.affiliation: Department of Dermatology, Faculty of Medicine, Oita University, Yufu, Japan.
authors.forename: Sakuhei
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Sano
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
authors.affiliation: Faculty of Medicine, Department of Dermatology, Kinki University, Osaka-Sayama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawada
authors.affiliation: Department of Dermatology, Juntendo University Urayasu Hospital, Urayasu, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suga
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: St John's Institute of Dermatology, King's College London, Guy's Hospital, London, England.
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
mesh_terms: D000293:Adolescent; D000328:Adult; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010916:Pityriasis Rubra Pilaris / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D053468:CARD Signaling Adaptor Proteins; D008565:Membrane Proteins; C426243:CARD14 protein, human; D006162:Guanylate Cyclase