Generalised pustular psoriasis
Gene: CARD14PMID: 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 ratingCreated: 29 Jun 2018, 5:33 p.m.
Comment on list classification: Changed from Red to Green from new publications to support the phenotypeCreated: 29 Jun 2018, 5:29 p.m.
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 psoriasisCreated: 4 Nov 2016, 1:33 p.m.
Comment on mode of pathogenicity: Gain of function / activating variantsCreated: 4 Nov 2016, 1:27 p.m.
Comment on phenotypes: Also associated with Pityriasis rubra pilaris, 173200Created: 4 Nov 2016, 1:20 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
generalised pustular psoriasis; pityriasis rubra pilaris
Publications
Phenotypes for gene: CARD14 were changed from CARD14 mediated psoriasis Psoriasis 2, 602723; Pityriasis rubra pilaris,173200; Other autoinflammatory diseases with known genetic defect to Psoriasis 2, OMIM:602723; Pityriasis rubra pilaris, OMIM:173200
Phenotypes for gene: CARD14 were changed from CARD14 mediated psoriasis Psoriasis 2, 602723 Pityriasis rubra pilaris,173200 Other autoinflammatory diseases with known genetic defect to CARD14 mediated psoriasis Psoriasis 2, 602723; Pityriasis rubra pilaris,173200; Other autoinflammatory diseases with known genetic defect
Phenotypes for gene: CARD14 were set to CARD14 mediated psoriasis Psoriasis 2, 602723 Pityriasis rubra pilaris,173200 Other autoinflammatory diseases with known genetic defect
Publications for gene: CARD14 were set to 26203641; 23648549; 22521418; 22703878; 23067081; 29704870; 29689250
Gene: card14 has been classified as Green List (High Evidence).
Promoted to V1 24/11/2016
This gene has been classified as Red List (Low Evidence).
Publications for CARD14 were set to 26203641
Mode of inheritance for CARD14 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity for CARD14 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Phenotypes for CARD14 were set to Psoriasis 2 602723
CARD14 was added to Generalised pustular psoriasispanel. Sources: Radboud University Medical Center, Nijmegen