TY - JOUR
T1 - Activating CARD14 Mutations are Associated with Generalised Pustular Psoriasis but Rarely Account for Familial Recurrence in Psoriasis Vulgaris
AU - Berki, Dorottya M
AU - Liu, Lu
AU - Choon, Siew-Eng
AU - David Burden, A
AU - Griffiths, Christopher Em
AU - Navarini, Alexander A
AU - Tan, Eugene S
AU - Irvine, Alan D
AU - Ranki, Annamari
AU - Ogo, Takeshi
AU - Petrof, Gabriela
AU - Mahil, Satveer K
AU - Duckworth, Michael
AU - Allen, Michael H
AU - Vito, Pasquale
AU - Trembath, Richard
AU - McGrath, John
AU - Smith, Catherine H
AU - Capon, Francesca
AU - Barker, Jonathan N
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84948712112&partnerID=8YFLogxK
U2 - 10.1038/jid.2015.288
DO - 10.1038/jid.2015.288
M3 - Article
C2 - 26203641
SN - 0022-202X
VL - 135
SP - 2964
EP - 2297
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
ER -