For more information on dermatology or #YaleMedicine, visit: https://www.yalemedicine.org/stories/rare-skin-problems-treatment-genetics.
We hear a lot about treatments for skin problems like an acne flare-up, a worrisome mole, or eczema. But there are also quite a few rare, severe skin conditions that can have a major impact on quality of life, whether because they are painful or make you self-conscious about your appearance. Also, skin disorders can affect other parts of the body as well. For instance, erythrokeratodermia-cardiomyopathy (EKC) syndrome is a condition that causes plaques to form on the skin and also heart abnormalities. And people with genetic skin diseases are much more likely to experience depression. “Most disorders have a genetic basis, and in skin diseases, it’s incredibly easy to see them,” says dermatologist Keith Choate, MD, PhD. The unique thing about skin diseases, he says, is that the entire skin is made up of the same cells, performing different roles depending on the location on the body. “When we find a mutation in a new gene, the first thing that we do is ask, ‘What is the normal function of this gene within the skin?”’ Dr. Choate uses genetics to diagnose and treat rare skin diseases. At Yale, over a dozen new genetic skin diseases have been defined, and in some cases, Dr. Choate’s group has been able to develop treatments for them. ac
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Decoding genetic skin disorders: lessons and new technologies
Air date: Wednesday, April 15, 2015, 3:00:00 PM
Category: WALS – Wednesday Afternoon Lectures
Runtime: 00:53:04
Description: NIH Director’s Wednesday Afternoon Lecture Series
The underlying molecular basis has been determined for more than 2,000 inherited monogenic disorders, of which at least 20 percent have cutaneous manifestations. The explosion of knowledge about genetics and genetic disease during the past 20 years has helped us to understand how gene changes translate into clinical manifestations. The current availability of whole exome sequencing (WES) is rapidly decoding rare genetic skin disorders, uncovering new causes, facilitating genotype-based diagnosis at a fraction of pre-next generation sequencing costs, and enabling new individualized therapies based on knowledge of the underlying gene mutation. Emerging therapeutic options include the use of topical gentamycin for “readthrough” of null mutations, replacement with recombinant protein, topical pathogenesis-based therapy for lipid biosynthesis defects, and cell-based therapies through grafting or stem cell transplantation. An exciting result of WES is the ability to decode somatic mosaic genetic disorders through the comparative analysis of DNA from a lesional skin biopsy and genomic DNA. Many of these mutations in mosaic disorders result from activation of the RAS or PI3K/AKT signaling pathways, allowing targeted topical therapy with small-molecule inhibitors or gene suppression. New technology, such as microneedles and topically applied nanoconjugate creams, promise to deliver antisense DNA or siRNA through the epidermal barrier to skin targets. Clinically normal skin in generalized recessive skin disorders may represent sites of revertant mosaicism, allowing expansion of the patient’s own phenotypically normal cells as replacement of abnormal cells with the risk of immune rejection. These therapeutic options, together with the plummeting cost of technology, will revolutionize our ability to provide personalized therapy for patients with genetic skin disorders.
For more information go to http://wals.od.nih.gov
Author: Amy S. Paller, M.S., M.D., Walter J. Hamlin Professor and Chair, Department of Dermatology; Professor, Department of Pediatrics, and Director, Skin Disease Research Center, Northwestern University Feinberg School of Medicine
Permanent link: http://videocast.nih.gov/launch.asp?18949
