Familial Pityriasis Rubra Pilaris Is Caused by Mutations in CARD14

Dana Fuchs-Telem, Ofer Sarig, Maurice A. M. van Steensel, Ofer Isakov, Shirli Israeli, Janna Nousbeck, Katharina Richard, Veronique Winnepenninckx, Marigje Vernooij, Noam Shomron, Jouni Uitto, Philip Fleckman, Gabriele Richard, Eli Sprecher*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

146 Citations (Web of Science)

Abstract

Pityriasis rubra pilaris (PRP) is a papulosquamous disorder phenotypically related to psoriasis. The disease has been occasionally shown to be inherited in an autosomal-dominant fashion. To identify the genetic cause of familial PRP, we ascertained four unrelated families affected by autosomal-dominant PRP. We initially mapped PRP to 17q25.3, a region overlapping with psoriasis susceptibility locus 2 (PSORS2 [MIM 602723]). Using a combination of linkage analysis followed by targeted whole-exome sequencing and candidate-gene screening, we identified three different heterozygous mutations in CARD14, which encodes caspase recruitment domain family, member 14. CARD14 was found to be specifically expressed in the skin. CARD14 is a known activator of nuclear factor kappa B signaling, which has been implicated in inflammatory disorders. Accordingly, CARD14 levels were increased, and p65 was found to be activated in the skin of PRP-affected individuals. The present data demonstrate that autosomal-dominant PRP is allelic to familial psoriasis, which was recently shown to also be caused by mutations in CARD14.
Original languageEnglish
Pages (from-to)163-170
JournalAmerican Journal of Human Genetics
Volume91
Issue number1
DOIs
Publication statusPublished - 13 Jul 2012

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