A Novel <i>PMVK </i>Variant Associated with Familial Porokeratosis

Abstract

<b><i>Background:</i></b> Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including phosphomevalonate kinase (PMVK) may alter this pathway, ultimately leading to porokeratosis. <b><i>Objectives:</i></b> The aim of the study was to identify the causative gene variant of porokeratosis in a Chinese family and investigate its population frequency and pathogenicity. <b><i>Method:</i></b> In this study, Sanger sequencing was used to identify the gene variant causative of porokeratosis; its population frequency was investigated by polymerase chain reaction-restriction fragment length polymorphism in 4 patients and three normal individuals as well as in 100 normal unrelated controls; finally, the pathogenicity of the mutation and the associated structural changes were predicted. <b><i>Results:</i></b> We identified a novel heterozygous missense variant, c.207G&gt;T (p. Lys69Asn) in the <i>PMVK</i> gene. This variant was found in all patients but not in the normal individuals in this family or in the 100 controls. In silico analysis indicated that the variant was pathogenic; p.Lys69Asn changed the length of the α-helix and the hydrogen bond pattern compared with the wild-type protein. <b><i>Conclusions:</i></b> The novel variant c.207G&gt;T (p. Lys69Asn) in the <i>PMVK</i> gene was the causative variant in this porokeratosis family. This finding provides further evidence for the genetic basis of this disease.