Detection of a novel missense mutation in the mevalonate kinase gene in one Chinese family with DSAP

Abstract

Disseminated superficial actinic porokeratosis (DSAP) is the most common form of porokeratosis and a severe chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. Recently, the mevalonate kinase (MVK) gene has been identified as a candidate gene responsible for DSAP and multiple mutations have been reported. Here, we report identification of a novel missense mutation in the MVK gene in a Chinese family with DSAP. A 50-year-old male was diagnosed as proband of DSAP based on the clinical and histological findings, which show numerous hyperpigmented macules by physical examination and cornoid lamella by skin biopsy. Similar skin symptoms were also observed in his father, who died many years ago. We prepared genomic DNA from the proband, unaffected individuals from his family members, as well as 100 unrelated healthy controls. PCR was then conducted using the above genomic DNA as template and the MVK gene-specific primers. The PCR product was subjected to direct sequencing and the sequence was compared to that of MVK gene within the NCBI database. We detected a heterozygous C to G transition at nucleotide 643 in exon 7 of MVK gene of the proband. This will result in an amino acid change at codon 215 (P.Arg215Gly.), which is from an arginine codon (CGA) to a Glycine codon (GGA). We did not detect any mutation in the unaffected family members or the 100 unrelated healthy controls, demonstrating that this is a novel missense mutation in MVK gene and therefore, contributes to the molecular diagnosis of DSAP.

Keywords: Disseminated superficial actinic porokeratosis; MVK gene; mutation.

Figure 1

Microscope and Histopathological examination. (A) Scattered, erythematous, annular plaques with slightly elevated borders were present on the upper extremities in the representative sporadic case. (B) Typical lesions with irregular annular and slightly elevated borders on the face were detected in the proband with DSAP of family one. (C) A biopsy of representative sporadic case shows that there is a focal thinning of the epidermis and a cornoid lamella in the upper part of the dermis. (D) A biopsy of the proband revealed a typical cornoid lamella in the epidermis. The granular layer was absent or decreased in this individual. Mild lymphocytic infiltration around the blood vessels in the upper dermis was present. The images (C, D) were visualized using hematoxylin and eosin (H&E) staining and are shown at either ×100 or ×400 magnifications, as indicated, and the images on the right is an enlarged version of the area in the box in the images on the left.

Figure 2

PCR result of exon 7. Column M is a DNA marker (DL2000), column 1 is one of the familial controls. Columns 2-5 are familial cases, with the sample in column 2 represents proband. Column 6-15 are sporadic cases, and the sample in column 6 is the representative sporadic case.

Figure 3

Mutation of case 1 and MVK gene structure. A: The sequencing result of exon 7 from control. B: The missense mutation of c.643C>G (exon 7) from proband. C: Genomic structure of human MVK gene. D: Four functional domains [peroxisome targeting signal (PTS) 2, ATP binding, and the two domains between them] and four amino acids (K13, E19, E193 and D204) are shown. UTR: untranslated region.