Identification of two novel MVD mutations and one novel FDPS mutation in Chinese patients with porokeratosis

Background Porokeratosis (PK) is an autosomal dominant inherited disorder characterized by abnormal epidermal keratinization, primarily resulting from mutations in four genes associated with the mevalonate pathway: mevalonate decarboxylase ( MVD ), mevalonate kinase ( MVK ), phosphomevalonate kinase ( PMVK ), and farnesyl diphosphate synthase ( FDPS ). Purpose The purpose of this study was to identify the causative mutations in seven sporadic cases of PK. Patients and methods Clinical data and blood samples were collected from these seven sporadic cases. To identify pathogenic gene mutations in the patients, both whole-exome and Sanger sequencing were conducted. Bioinformatics resources such as PROVEAN, SIFT, PolyPhen-2, and Mutation Taster were employed to assess the pathogenicity of the identified mutations. Results This study included seven sporadic cases of PK, comprising two cases of disseminated superficial actinic porokeratosis (DSAP), and five cases of disseminated superficial porokeratosis (DSP). We identified a total of five heterozygous mutations, including two novel MVD mutations (c.1122 + 1G > A, c.576G > T), one novel FDPS mutation (c.986A > C), and two MVD mutations that have been reported previously (c.1A > G and c.746 T > C). In conjunction with our previous study, we identified a total of six patients with the MVD c.746 T > C mutation from Jiangxi province, China, representing 50% of the total MVD mutation cases (12 in total). Conclusion This research has expanded the database of mevalonate pathway genes associated with PK, thereby improving our comprehension of the fundamental mechanisms involved.