Genetic Mutation Triggers Inherited Skin Disorder

A team of researchers have found a strong genetic evidence of a link between mutations of the mevalonate kinase gene (MVK) and disseminated superficial actinic porokeratosis (DSAP) , a skin disease.

This link has been discovered by a Chinese team led by Anhui Medical University and BGI. This new discovery is a step towards the genetic pathogenesis of DSAP. And also highlights the further molecular diagnosis and treatment.

This study was carried online in the Nature Genetics.

DSAP is an inherited skin condition causing dry patches on arms and legs. It is a rare non cancerous and non contagious skin disorder. This chronic disorder can be treated, but it cannot be cured.

To identify the MVK mutations, researchers conducted Sanger sequencing in other DSAP cases. And none of which was detected in 676 unrelated and ethnically matched controls. It provided strong evidence that these novel mutations were not polymorphisms. They did not find MVK mutations in other clinical subtypes of Porokeratosis, suggesting that MVK mutations may be specific to DSAP patients.

MVK is an important enzyme in the mevalonate pathway that is vital for multiple cellular processes by providing cells with essential bioactive molecules. 

Tao Jiang, senior scientist of this project at BGI, said, "Considering the high genetic heterogeneity of DSAP, It is fortunate for us to find the causative gene MVK by sequencing only three exomes and using previous genome-wide linkage results. Our study provides new insights into the pathogenesis of DSAP, and the identified MVK mutations offer the best candidate targets for gene diagnosis and clinical treatment of the disease."

Xuejun Zhang, corresponding author of this study, President of Anhui Medical University, said, "The exome sequencing is an effective method for identifying disease gene of monogenetic diseases in recent years. In this study, the Chinese scientists found disease gene MVK for DSAP using exome sequencing plus functional study. It not only indicates China has step into the most advanced level in searching the disease genes for monogenetic disease in the world, but also provides scientific basis for revealing DSAP pathogenesis, genetic counseling, risk prediction, prenatal diagnosis, new drug development, clinical diagnosis and treatment."