Familial Pityriasis Rubra Pilaris (PRP) via the CARD14 Gene

Pityriasis rubra pilaris (PRP) is a papulosquamous disease characterized by keratotic follicular papules, and salmon-colored skin rash covered in fine scales. Major clinical features include widespread erythematous plaques, follicular plugging, and palmoplantar keratoderma. PRP occurs 1 in 5,000 individuals, and the majority of cases are simplex. Familial cases are rare (~6.5% of all affected PRP cases) and may show early age of onset, incomplete penetrance, and variable expression (Fuchs-Telem et al. 2012).

Pathogenic variants in the CARD14 gene cause autosomal dominant pityriasis rubra pilaris. The CARD14 protein is an activator of nuclear factor kappa B signaling which plays a key role in immune responses and inflammatory reactions. To date, somewhat more than 10 unique pathogenic variants have been reported. Nearly 80% of reported variants are missense with three splicing and a small in-frame deletion also having been reported (Fuchs-Telem et al. 2012; Inoue et al. 2016). No large deletions or duplications have been reported (Human Gene Mutation Database).

In one small study, three unique CARD14 causative variants were found in 4 unrelated families affected with familial pityriasis rubra pilaris who were diagnosed based on both clinical and skin biopsy findings (Fuchs-Telem et al. 2012).

No large deletions and duplications involving CARD14 have been reported (Human Gene Mutation Database).

This test provides full coverage of all coding exons of the CARD14 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).