LAUSR

Porokeratosis (OMIM 175800) is a heterogeneous group of keratinization disorders that exhibit an autosomal dominant mode of inheritance. Currently, there are around 20 clinical variants of PK in the English literature, which are classified by their clinical manifestations, including lesion number, size, morphology and distribution. In our previous study, only six different pathogenic mutations of the gene for phosphomevalonate kinase (PMVK) gene (MIM 607622) were found in patients with classic porokeratosis of Mibelli. In the current study, we identified a novel missense variation c.314T>C (p. Leu105Pro) in the PMVK gene in one Chinese family with porokeratosis of Mibelli (PM) who were from Hunan province. A 50-year-old man presented with a 35-year history of annular keratotic papules or plaques on his face, trunk, buttock (Fig. 1a) and extremities. His penis and scrotum were also involved. Similar lesions were found in the proband’s father and daughter. Histological examination of a biopsy specimen obtained from the right leg revealed an invagination of the epidermis, containing a column of porakeratotic cells overlying the absence of a granular layer (Fig. 1b). Genetic studies were carried out after approval by the ethics committee of Fudan University and provision of informed consent from the participants. Peripheral blood samples were taken from the proband and from his wife and daughter. All exons and flanking intronic sequences of PMVK (NM_006556.3) were amplified by PCR, and the PCR products were purified and sequenced on an automated sequencer (ABI 3730xl; Applied Biosystems, Foster City, CA, USA). Sequence analysis showed a heterozygous T>C transition at nucleotide 314 in exon 4 of PMVK in the proband (Fig. 2a), which was also detected in his daughter but not in his wife or in 96 unrelated healthy controls. We were pleased to read the recent publications by Wang et al. and Li et al., whose findings support and supplement our previous findings. Using whole-exome sequencing, the nonsense variation c.412C>T (p.Arg138*) in PMVK was also identified in two Chinese families with porokeratosis. In that study, both Figure 1b and supplementary Figure 1b3 showed the clinical phenotypes of classic PM, not disseminated superficial porokeratosis. Moreover, one novel mutation of PMVK (c.143G>A) was identified in one patient with genital porokeratosis without family history; however, the description of this mutation appears to have been a clerical error and should have been stated as c.143A>G (p.Lys48Arg). (a)