Generalised pustular psoriasis

Gene: CARD14

PMID: 29689250 reported that heterozygous mice harboring a CARD14 gain-of-function mutation spontaneously develop a chronic psoriatic phenotype with characteristic scaling skin lesions, epidermal thickening, keratinocyte hyperproliferation, hyperkeratosis and immune cell infiltration. Spoerri et al. (2018) PMID: 29704870 Psoriasis susceptibility (PSORS)2 and pityriasis rubra pilaris (PRP) are both monogenic autoinflammatory diseases. Both phenotypes have been associated to CARD14 variants (PMID:23648549;22521418; 22703878; 2306708). CARD14 is an epidermal regulator of NF-κB transcription factor, variants in CARD14 initiate a process that includes inflammatory cell recruitment by keratinocytes and perpetuate a vicious cycle of epidermal inflammation and regeneration that cause the abnormal keratinization. c.349G > A, p.Gly117Ser is the the most prevalent variant, and c.413A > C, p.Glu138Ala (a de novo mutation) were shown to lead to enhanced NF-kB activation and upregulation of a subset of psoriasis-associated genes in keratinocytes (PMID:22521418).
The most prevalent pathogenic variant is c.349G>A, p.Gly117Ser, which has been reported in a number of unrelated families and ethnicities PMID:23648549;22521418; 22703878; 2306708.Although most of the cases of Psoriasis are sporadic and acquired, a familial form of the disease exists. The rare familial cases show autosomal dominant inheritance with incomplete penetrance and variable expression. Psoriasis is a chronic immune-mediated inflammatory disease of the skin, this panel includes Autoinflammatory disorders.

Created: 29 Jun 2018, 5:33 p.m.

Comment on publications: added publications to support to Green rating

Created: 29 Jun 2018, 5:33 p.m.

Comment on list classification: Changed from Red to Green from new publications to support the phenotype

Created: 29 Jun 2018, 5:29 p.m.

Red List (low evidence)

Comment when marking as ready: Associated with phenotype in OMIM, not in G2P / DD. At least 5 variants reported Psoriasis 2 602723, but only in one case did the phenotype include pustular psoriasis

Created: 4 Nov 2016, 1:33 p.m.

Comment on mode of pathogenicity: Gain of function / activating variants

Created: 4 Nov 2016, 1:27 p.m.

Comment on phenotypes: Also associated with Pityriasis rubra pilaris, 173200

Created: 4 Nov 2016, 1:20 p.m.

Red List (low evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
generalised pustular psoriasis; pityriasis rubra pilaris

Publications

• 26203641