Scientists discover mevalonate kinase gene mutations associated with disseminated superficial actinic porokeratosis

September 16, 2012

A Chinese research team, led by Anhui Medical University and BGI, has found the strong genetic evidences of mevalonate kinase gene (MVK) mutations link to disseminated superficial actinic porokeratosis (DSAP). It is a major step toward discovering the genetic pathogenesisof DSAP, and sheds an eye-opening insight into its further molecular diagnosis and treatment. The latest study was published online in Nature Genetics.

DSAP is a rare, non-cancerous, non-contagious skin disorderthat causes dry, itchy lesions on the arms and legs. It usually begins to develop in adolescents and reach near-complete penetrance by the third or fourth decade of life. The accumulated is a risk factor for DSAP. DSAP is a ; it can be treated, but it cannot be cured.

In this study, Chinese researchers performed exome sequencing in two affected and one unaffected individuals who belong to a DSAP family. Through variants analysis and data filtering, they supposedthat MVK gene emerged as the only located in previously defined linkage region linked to DSAP. Then they confirmed the co-segregation between the identified novel deleterious mutation and DSAP phenotype within the family.

To further identify novel MVK mutations, researchers conducted Sanger sequencing in other DSAP cases, which identified additional novel deleterious mutations. 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 found MVK mutations in other clinical subtypes of Porokeratosis, suggesting that MVK mutations may be specific to DSAP patients.

Mevalonate kinase, the protein encoded by MVK, is an important enzyme in the mevalonate pathway that is vital for multiple by providing cells with essential bioactive molecules. In the investigation of the impact of MVK expression on the biological activities of keratinocytes, researchers indicated thatMVK plays a role in regulating calcium-induced keratinocytes differentiation and the MVK expression could protect keratinocytes from UVA-caused apoptosis.

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 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 searchingthe disease 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."

Explore further: New inherited neurometabolic disorder discovered

Related Stories

New inherited neurometabolic disorder discovered

September 30, 2011
Researchers at the Swedish medical university Karolinska Institutet have discovered a new inherited disorder that causes severe mental retardation and liver dysfunction. The disease, adenosine kinase deficiency, is caused ...

Mutations in 3 genes linked to autism spectrum disorders

April 4, 2012
Mutations in three new genes have been linked to autism, according to new studies including one with investigators at Mount Sinai School of Medicine. All three studies include lead investigators of the Autism Sequencing Consortium ...

As new data wave begins, a gene study in one disease discovers mutations in an unrelated disease

July 20, 2011
Often enough, in science as in life, unexpected knowledge has a personal impact. Researchers seeking rare gene variants in just a few individuals with attention-deficit hyperactivity disorder (ADHD) discovered that one patient ...

Clarity begins at exome: Sequencing protein-making part of genome can change diagnosis and patient care

June 13, 2012
In the June 13 issue of Science Translational Medicine, an international team led by researchers from the University of California, San Diego School of Medicine reports that the new technology of exome sequencing is not only ...

Recommended for you

New gene editing approach for alpha-1 antitrypsin deficiency shows promise

October 20, 2017
A new study by scientists at UMass Medical School shows that using a technique called "nuclease-free" gene editing to correct cells with the mutation that causes a rare liver disease leads to repopulation of the diseased ...

Maternal diet may program child for disease risk, but better nutrition later can change that

October 20, 2017
Research has shown that a mother's diet during pregnancy, particularly one that is high-fat, may program her baby for future risk of certain diseases such as diabetes. A new study from nutrition researchers at the University ...

Researchers find evidence of DNA damage in veterans with Gulf War illness

October 19, 2017
Researchers say they have found the "first direct biological evidence" of damage in veterans with Gulf War illness to DNA within cellular structures that produce energy in the body.

Researchers drill down into gene behind frontotemporal lobar degeneration

October 19, 2017
Seven years ago, Penn Medicine researchers showed that mutations in the TMEM106B gene significantly increased a person's risk of frontotemporal lobar degeneration (FTLD), the second most common cause of dementia in those ...

New clues to treat Alagille syndrome from zebrafish

October 18, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies potential new therapeutic avenues for patients with Alagille syndrome. The discovery, published in Nature Communications, ...

Genetic variants associated with obsessive-compulsive disorder identified

October 18, 2017
(Medical Xpress)—An international team of researchers has found evidence of four genes that can be linked to obsessive-compulsive disorder (OCD). In their paper published in the journal Nature Communications, the group ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.