Activating CARD14 Mutations Are Associated with Generalized Pustular Psoriasis but Rarely Account for Familial Recurrence in Psoriasis Vulgaris.
- Berki DM Department of Medical and Molecular Genetics, King's College London, London, UK.
- Liu L St John's Institute of Dermatology, King's College London, London, UK.
- Choon SE Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Malaysia.
- David Burden A Department of Dermatology, University of Glasgow, Glasgow, UK.
- Griffiths CEM Department of Dermatology, University of Manchester, Manchester, UK.
- Navarini AA Department of Dermatology, Zurich University Hospital, Zurich, Switzerland.
- Tan ES National Skin Centre, Singapore, Singapore.
- Irvine AD Paediatric Dermatology, Our Lady's Children's Hospital, Dublin, Ireland; Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
- Ranki A Department of Dermatology, Venereology and Allergic Disease, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
- Ogo T Department of Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan.
- Petrof G St John's Institute of Dermatology, King's College London, London, UK.
- Mahil SK Department of Medical and Molecular Genetics, King's College London, London, UK.
- Duckworth M St John's Institute of Dermatology, King's College London, London, UK.
- Allen MH St John's Institute of Dermatology, King's College London, London, UK.
- Vito P Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, Italy.
- Trembath RC Queen Mary, University of London, Barts and The London School of Medicine and Dentistry, London, UK.
- McGrath J St John's Institute of Dermatology, King's College London, London, UK.
- Smith CH St John's Institute of Dermatology, King's College London, London, UK.
- Capon F Department of Medical and Molecular Genetics, King's College London, London, UK. Electronic address: francesca.capon@kcl.ac.uk.
- Barker JN St John's Institute of Dermatology, King's College London, London, UK. Electronic address: jonathan.barker@kcl.ac.uk.
- 2015-07-24
Published in:
- The Journal of investigative dermatology. - 2015
CARD Signaling Adaptor Proteins
Female
Guanylate Cyclase
Humans
Male
Membrane Proteins
Mutation
NF-kappa B
Protein Multimerization
Psoriasis
Recurrence
English
Caspase recruitment family member 14 (CARD14, also known as CARMA2), is a scaffold protein that mediates NF-κB signal transduction in skin keratinocytes. Gain-of-function CARD14 mutations have been documented in familial forms of psoriasis vulgaris (PV) and pityriasis rubra pilaris (PRP). More recent investigations have also implicated CARD14 in the pathogenesis of pustular psoriasis. Follow-up studies, however, have been limited, so that it is not clear to what extent CARD14 alleles account for the above conditions. Here, we sought to address this question by carrying out a systematic CARD14 analysis in an extended patient cohort (n=416). We observed no disease alleles in subjects with familial PV (n=159), erythrodermic psoriasis (n=23), acral pustular psoriasis (n=100), or sporadic PRP (n=29). Conversely, our analysis of 105 individuals with generalized pustular psoriasis (GPP) identified a low-frequency variant (p.Asp176His) that causes constitutive CARD14 oligomerization and shows a significant association with GPP in Asian populations (P=8.4×10(-5); odds ratio=6.4). These data indicate that the analysis of CARD14 mutations could help stratify pustular psoriasis cohorts but would be mostly uninformative in the context of psoriasis and sporadic PRP.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1038/jid.2015.288
- PMID 26203641
- Persistent URL
- https://sonar.ch/global/documents/12931
Statistics
Document views: 42
File downloads:
- Full-text: 0