Anhui Medical University in China makes important discovery

STORY: Sept 16, 2012 - A team of researchers at Anhui Medical University in China and BGI, has found strong evidence that there is a link between mutations of the mevalonate kinase gene (MVK) and DSAP. It is a major step toward discovering the genetic mechanism that causes DSAP, and sheds light on its further molecular diagnosis and treatment. According to Tao Jiang "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."

According to Xuejun Zhang, President of Anhui Medical University, this study "provides scientific basis for revealing DSAP pathogenesis, genetic counseling, risk prediction, prenatal diagnosis, new drug development, clinical diagnosis and treatment." It is comforting to know that research is actually going on to find a cure for DSAP!

Here's an older genetic study that appears to have narrowed the problematic gene to within 122 locations. Is the MVK gene within these locations? If anyone reading this knows, let me know.

Disseminated superficial actinic porokeratosis is an autosomal dominant cutaneous disorder characterized by many uniformly small, minimal, annular, anhidrotic, and keratotic lesions. The genetic basis for this disease is unknown. Using a genomewide search in a large Chinese family, we identified a locus at chromosome 12q23.2-24. 1 responsible for disseminated superficial actinic porokeratosis. The fine mapping study indicates that the disseminated superficial actinic porokeratosis gene is located within a 9.6 cM region between markers D12S1727 and D12S1605, with a maximum two-point LOD score of 20.53 (theta = 0.00) at D12S78. This is the first locus identified for a genetic disease where the major phenotype is porokeratosis. The study provides a map location for isolation of a gene causing disseminated superficial actinic porokeratosis.

In the late 60's a researcher discovered that DSAP is probably an autosomal hereditary disorder. This means there is a 50/50 chance of inheriting the bad DSAP gene if ONE parent has it. If both parents have it there is a 75% chance of inheriting the defective gene. Remember that one may have the bad gene but never develop DSAP lessions if they habitually avoid the sun, live in long-sleeve climates, etc.

This study of DSAP lesion material shows altered DNA ploidy, chromosomal instability, and abnormal overxpression of tumor suppressor p53 protein.

Chernosky ME, Freeman RG – Arch Dermatol. 1967; 96:611-624

Magee JW, McCalmont TH, LeBoit PE. Overexpression of p53 tumor suppressor protein in porokeratosis. Arch Dermatol. 1994; 130: 187-190

Back around 2000, I posed some questions to a researcher at the University of Michigan who was conducting research on other skin related disorders:

QUESTION: Are you aware of any DSAP research going on?

ANSWER: I am not aware of any genetic research on DSAP. The major difficulties in researching other skin diseases are availability of a sufficient number of families (which sometimes need to be in the dozens or hundreds) and funding. It is not easy to get research grants unless the disease affects a significant fraction of the population. Finding entire families where everyone is willing to donate blood samples and subject themselves to evaluation is also not easy. In addition researchers need to convince funding agencies that they are able to pay enough attention to all the things they do. This limits the number of projects that can be managed in a laboratory. Diseases for which there are consumer advocate groups seem to get more attention from funding agencies.

QUESTION: How much $$ does it take to start a research project?

ANSWER: About 2 million US.

It will probably take someone really wealthy to do further genetic studies on DSAP. In the mean time, I am trying to gather email addresses of people with DSAP. It reasons that researchers might contact me if they are looking for people with DSAP to study.