Identification of three mutations in the MVK gene in six patients associated with disseminated superficial actinic porokeratosis

• Two novel mutations for DSAP c.31C > T (P11S) and c.1004G > A (G335D) in MVK gene were identified.
• The three mutant MVK proteins identified in this study were less stable than the wild type protein in different degrees.
• Mutation G335D resulted in the misfolding of the ATP binding domain.

Porokeratosis is recognized as a heterogenously inherited epidermal keratinization disorder. Disseminated superficial actinic porokeratosis (DSAP) is considered to be the most common form of porokeratosis and is characterized by multiple, small keratotic lesions on sun-exposed areas of body. MVK has been reported to be the main candidate gene associated with DSAP. In this study, six sporadic cases of DSAP were clinically characterized. Direct DNA sequencing analysis of the whole coding regions of MVK detected three MVK missense mutations, and two were novel for DSAP: c.31C > T (P11S) and c.1004G > A (G335D). The three mutant MVK proteins were less stable than the wild type protein in different degrees. Mutation G335D also resulted in the misfolding of the ATP binding domain. This study extends the mutation spectrum of MVK. MVK protein stability and correct folding might be the molecular mechanism causing DASP. A 50% probability of detecting a MVK mutation in six DSAP sporadic cases indicated that the MVK gene was useful for clinical characterization, genetic counseling and prenatal diagnosis of DSAP.