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Activating CARD14 Mutations are Associated with Generalised Pustular Psoriasis but Rarely Account for Familial Recurrence in Psoriasis Vulgaris

Research output: Contribution to journalArticle

Dorottya M Berki, Lu Liu, Siew-Eng Choon, A David Burden, Christopher Em Griffiths, Alexander A Navarini, Eugene S Tan, Alan D Irvine, Annamari Ranki, Takeshi Ogo, Gabriela Petrof, Satveer K Mahil, Michael Duckworth, Michael H Allen, Pasquale Vito, Richard Trembath, John McGrath, Catherine H Smith, Francesca Capon, Jonathan N Barker

Original languageEnglish
Pages (from-to)2964–297
JournalJournal of Investigative Dermatology
Volume135
Early online date23 Jul 2015
DOIs
Publication statusPublished - 13 Aug 2015

King's Authors

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=105) or sporadic pityriasis rubra pilaris (n=29). Conversely, our analysis of 100 individuals with generalised pustular psoriasis (GPP) identified a low-frequency variant (p.Asp176His) which causes constitutive CARD14 oligomerization and shows significant association with GPP in Asian populations (P=8.4 × 10(-5); OR=6.4). These data indicate that the analysis of CARD14 mutations could help to stratify pustular psoriasis cohorts but would be mostly uninformative in the context of psoriasis and sporadic pityriasis rubra pilaris.Journal of Investigative Dermatology accepted article preview online, 23 July 2015. doi:10.1038/jid.2015.288.

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