The PER3rs772027021 SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria

In this study, whole-exome sequencing, data analysis, and Sanger sequencing were utilized for a four-generation extended Chinese family with DUH. A single-nucleotide polymorphism (SNP) (c. 517C  >  T (p.P173S), rs772027021) variant in exon 5 ofPeriod Circadian Regulator 3 (PER3) (NM_001289861) was detected in each affected individual of the DUH family; the c. 517C  >  T SNP ofPER3 (PER3rs772027021 SNP) and a novel mutation in exon 14 ofSASH1 (c. 1574C  >  G (p.T525R)) were both found in the proband. The affected individuals carryingPER3rs772027021 SNP in this family demonstrated mild-pigmented phenotypes compared to those of the proband carryingPER3rs772027021 SNP andSASH1T525R mutation. Increased melanin synthesis was induced byPER3rs772027021 SNP in the melanocytes of affected epithelial tissues. MutatedSASH1 orPER3rs772027021 SNP alone or cooperation of mutation ofSASH1 andPER3rs772027021 SNP synergistically led to increased melanin synthesis and enhanced proliferation of melanoma cells in vitro. We also phenotypically characterized a commercially available zebrafish mutant line harboring thePER3rs772027021 SNP to induce melanocyte proliferation in vivo. Our results are the first to reveal that thisPER3 SNP may be pathogenic for a novel DUH subtype with mild hyperpigmented and/or hypopigmented phenotypes and that mutation ofSASH1 andPER3 cooperatively promotes hyperpigmentation phenotypes.Key messagesPER3  rs772027021 SNP is identified to be associate...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research