PSORS2 is Due to Mutations in CARD14

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Catherine Jordan et al are reporting in The American Journal of Human Genetics their study which “concludes a 17 year search for PSORS2”. PSORS2 is one of the loci identified in multiple GWAS and linkage studies as a risk locus for psoriasis and after sequencing of the genes in the identified chromosomal interval; ZNF750 was designated as the most probable disease causing gene. Jordan et al have reanalyzed the original families along with a young patient with a very severe, early-onset psoriasis (6 months of age) by a combination of targeted DNA capture and high-throughput sequencing and have identified CARD14 as the gene responsible for the disease. Their findings are backed up by functional data both in vitro and in vivo showing that CARD14 mutations increase NF-kB activation leading to the upregulation of transcripts such as IL8 and CCL20 which ultimately create the vicious cycle of inflammation and acanthosis that characterizes psoriasis. Additionally in a second study the identified 15 additional variants in patients with psoriasis and identified a possible link with HLA-Cw*0602.

Periklis Makrythanasis, MD, PhD

OMMBID Part 27: SKIN, Chapter 222.1: Genetics of Psoriasis

Jordan CT et al; PSORS2 is due to mutations in CARD14.; Am J Hum Genet. 2012 May 4;90(5):784-95. Epub 2012 Apr 19.; PMID: 22521418

Jordan CT et al; Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis.;  Am J Hum Genet. 2012 May 4;90(5):796-808. Epub 2012 Apr 19.; PMID: 22521419


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