A Novel PMVK Variant Associated with Familial Porokeratosis

• Published in: Human heredity Vol. 88; no. 1; pp. 50 - 57
• Main Authors: Zhang, Wenjing, Nie, Xinmiao, Shi, Lei, Shao, Fengmin, Cao, Lihua
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2023
• Subjects: Amino acids; Analysis; Brief Report; DNA sequencing; Enzymes; Ethylenediaminetetraacetic acid; Genetic aspects; Humans; Hydrogen; Mutation; Mutation, Missense; Nucleotide sequencing; Pedigree; Phosphotransferases (Phosphate Group Acceptor) - genetics; Porokeratosis - genetics; Skin; Skin diseases; China; PMVK gene; Porokeratosis; Variation; Phosphomevalonate kinase; Mevalonate pathway
• DOI: 10.1159/000531120
• ISSN: 0001-5652; 1423-0062

Background: 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. Objectives: 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. Method: 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. Results: We identified a novel heterozygous missense variant, c.207G>T (p. Lys69Asn) in the PMVK 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. Conclusions: The novel variant c.207G>T (p. Lys69Asn) in the PMVK gene was the causative variant in this porokeratosis family. This finding provides further evidence for the genetic basis of this disease.