Increased epidermal expression and absence of mutations inCARD14in a series of patients with sporadic pityriasis rubra pilaris

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

“…The subsequent analysis of the pityriasis rubra pilaris cohort generated similarly negative results, validating the emerging notion that CARD14 mutations do not contribute to sporadic forms of the disease (Eytan et al, 2014). While the idea that CARD14 plays a role in the pathogenesis of PV and PRP is supported by observations of gene over-expression in patient skin and by the results of genome-wide association studies (Eytan et al, 2014;Tsoi et al, 2012), our findings indicate that screening this locus for deleterious mutations is unlikely to help the stratification of patient resources.…”

“…While the idea that CARD14 plays a role in the pathogenesis of PV and PRP is supported by observations of gene over-expression in patient skin and by the results of genome-wide association studies (Eytan et al, 2014;Tsoi et al, 2012), our findings indicate that screening this locus for deleterious mutations is unlikely to help the stratification of patient resources.…”

“…CARD14 mutations do not play a significant role in the pathogenesis of familial PV, sporadic pityriasis rubra pilaris or acral pustular psoriasis Since all CARD14 mutations described to date cluster to exons 3 and 4 (Eytan et al, 2014;FuchsTelem et al, 2012;Jordan et al, 2012b;Sugiura et al, 2014), we initially focused our genetic screening on this region. We sequenced the two exons in a total of 416 patients, affected by acral pustular psoriasis (APP; n=100), erythrodermic psoriasis (n=23), familial PV (n=159), generalised pustular psoriasis (n=105) or pityriasis rubra pilaris (n=29) ( Table 1, Supplementary Table 1).…”

“…Likewise, studies of CARD14 in PRP have mostly been restricted to cohorts recruited in the Middle East (Eytan et al, 2014) and the association between p.Asp176His and generalised pustular psoriasis has yet to be validated, as it was only supported by marginal statistical significance. Thus, large gaps remain in our understanding of the phenotypes that are caused by CARD14 mutations and it is not clear whether the genetic analysis of this locus might aid disease stratification.…”

Analysis of CARD14 Polymorphisms in Pityriasis Rubra Pilaris: Activation of NF-κB

“…This is consistent with a recent study wherein CARD14 mutations were undetectable in 8 cases of sporadic PRP (Hong et al , 2014). However, recent studies on sporadic PRP, similar to sporadic psoriasis, have suggested that NF-κB signaling is activated in the epidermis of patients with PRP, even in the absence of pathogenic CARD14 mutations (Eytan et al , 2014a). There could be several explanations for the lack of identifiable mutations in the CARD14 gene in most sporadic cases of PRP despite apparent activation of NF-κB.…”