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J Invest Dermatol. 2015 Dec;135(12):2964-2970. doi: 10.1038/jid.2015.288. Epub 2015 Jul 23.

Activating CARD14 Mutations Are Associated with Generalized Pustular Psoriasis but Rarely Account for Familial Recurrence in Psoriasis Vulgaris.

Author information

1
Department of Medical and Molecular Genetics, King's College London, London, UK.
2
St John's Institute of Dermatology, King's College London, London, UK.
3
Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Malaysia.
4
Department of Dermatology, University of Glasgow, Glasgow, UK.
5
Department of Dermatology, University of Manchester, Manchester, UK.
6
Department of Dermatology, Zurich University Hospital, Zurich, Switzerland.
7
National Skin Centre, Singapore, Singapore.
8
Paediatric Dermatology, Our Lady's Children's Hospital, Dublin, Ireland; Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
9
Department of Dermatology, Venereology and Allergic Disease, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
10
Department of Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan.
11
Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, Italy.
12
Queen Mary, University of London, Barts and The London School of Medicine and Dentistry, London, UK.
13
Department of Medical and Molecular Genetics, King's College London, London, UK. Electronic address: francesca.capon@kcl.ac.uk.
14
St John's Institute of Dermatology, King's College London, London, UK. Electronic address: jonathan.barker@kcl.ac.uk.

Abstract

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.

PMID:
26203641
DOI:
10.1038/jid.2015.288
[Indexed for MEDLINE]
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