Identifying Six Novel Genetic Variants and Alterations in Peripheral T-cell Subsets in Porokeratosis Patients

Abstract Porokeratosis (PK) is considered a skin-specific autoinflammatory keratinization disease. Intriguingly, four causative genes of PK are in turn arranged in mevalonate pathway, with MVD variants being the commonest followed by MVK variants in a cohort of Chinese patients. Based on our previous findings, PK patients with MVK or MVD variants show different phenotypes. Using targeted exome sequencing and exonic CNV screening, we identified 14 mutations in the 26 PK patients, including six novel mutations (MVK: c.118_226 + 1337dup, c.388_392delGATATinsC, c.613A > T, c.768G > C, and MVD: c.250C > T, c.988T > G). Peripheral T-cell subsets were analyzed by flow cytometry in PBMCs from 22 PK patients with MVK or MVD variants and 27 normal controls (NCs). In contrast to NCs, significantly decreased frequencies of CD8+ and Vγ9Vδ2 T cells were observed in the PK patients with MVD variants. Moreover, it was found that dysregulated secretion of pro-inflammatory cytokines by T-cell in both PK patients with MVK and MVD variants. Collectively, our findings enriched the Human Gene Mutation Databases and provided the cues to further studies on autoreactive CD8 + T and γδT cells in the pathogenesis of PK.