Two Novel and Three Recurrent Mutations in the Mevalonate Pathway Genes in Chinese Patients with Porokeratosis

Abstract

Purpose

Porokeratosis (PK) is a chronic autosomal-dominant cutaneous keratinization disorder exhibiting clinical and genetic heterogeneity. Mevalonate decarboxylase (MVD), farnesyl diphosphate synthase (FDPS), phosphomevalonate kinase(PMVK), and mevalonate kinase genes(MVK), which encode the mevalonate pathway, are disease-causing genes in PK.

Patients and Methods

Data and blood samples were collected from two Chinese families and five sporadic patients with porokeratosis. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients.

Results

Five heterozygous mutations were identified, including a novel FDPS stop-gain mutation c.438T>G (p.Tyr146Ter), a novel MVD missense mutation c.683G>C (p.R228P), and three previously reported MVD mutations: c.746T>C (p.F249S), c.875A>G (p.N292S), and c.1111_1113del (p.371_371del). The novel FDPS c.438T>G mutation was predicted as “disease-causing” (p = 1) by Mutation Taster. The other novel MVD c.683G>C was also predicted as “deleterious” (score = 0.00) by Sorting Intolerant From Tolerant (SIFT), “probably damaging” (score = 1) by PolyPhen2, and “disease-causing” (p = 0.999) by Mutation Taster.

Conclusion

Our results extended the mutation spectrum of mevalonate pathway genes in porokeratosis and provided useful strategies for a more accurate diagnosis and genetic counseling.

Keywords:

• porokeratosis
• mutation
• MVD
• FDPS
• genetics

Data Sharing Statement

All the data used for the analyses in this study are available from the corresponding author upon reasonable request. The mutations identified in this study can be found in the GenBank online repositories (accession numbers: OR354918, OR354919, OR354920, OR354921, OR354922, https://www.ncbi.nlm.nih.gov/genbank/).

Ethics Approval and Consent to Participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of the Second Affiliated Hospital of Nanchang University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. The authors affirm that human research participants provided informed consent for publication of the images in Figure 1.

Acknowledgments

We thank all patients and their family members for participating in this study.

Disclosure

The authors have no relevant financial or non-financial interests to disclose for this work.

Additional information

Funding

This study was funded by the National Natural Science Foundation of China (Project No. 81960569) and the Natural Science Foundation of Jiangxi Province (Project No. 20232BAB206126).