A promoter sequence variant of ZNF750 is linked with familial psoriasis

We previously mapped a psoriasis-susceptibility gene to a 3.8-Mb region of the 17q terminus in a five-generation Chinese family with autosomal-dominant psoriasis. To identify the mutations responsible for the psoriasis in this family, we sequenced 78 genes within the region and found four gene variants, p.Ala201Val in CD7, c.-625A>C in zinc-finger protein 750 (ZNF750), p.Asp189Asn in C17orf56, and p.Ala568Thr in AATK cosegregated with the disease. The latter two variants were not studied further in the absence of disease segregation in other familial psoriasis and presence of variants in normal subjects. Functional analyses of CD7 did not support CD7 as a disease-causing gene. In contrast, the c.-625A>C mutation in ZNF750 resulted in a 42% reduction of the promoter activity, and the electrophoretic mobility shift assay showed binding of nuclear protein(s) to the mutant C allele. The c.-625A>C mutation was found in another sporadic psoriasis patient but was absent in 188 normal controls. Together, the mutation accounts for 1.7% (confidence interval: 0.2-5.84%) of psoriasis in the Chinese population. This report suggests that ZNF750 mutations could contribute to psoriasis susceptibility.