Cause Of, And Possible Cure For, Genetic Skin Disorder

Cause Of, And Possible Cure For, Genetic Skin Disorder

ArticlePress release
Skin Care
Current Medical News
+1
Contributed byKrish Tangella MD, MBAJun 05, 2017

Yale scientists have discovered the cause of a disfiguring skin disorder and determined that a commonly used medication can help treat the condition.

About one in 200,000 people are affected by a group of severe skin disorders known as the ichthyoses (ik-thee-oh-sees), which feature dry, scaly, or thickened skin. Although treatment with topical medications can help, there is no cure. To better understand the cause of such skin disorders, a Yale-led research team studies the genes of individuals affected by the conditions.

Mutations underlying most types of ichthyosis have been identified, but roughly 15% of cases have unexplained origins, said associate professor of dermatology and senior author Dr. Keith Choate. To uncover potential new causes, the research team initially sequenced patients' exomes (the protein-coding portions of the genome). They identified mutations in the gene KDSR that prevent the skin from producing ceramides -- fat molecules that seal the skin and protect it from water loss. Ceramides are naturally generated by the body, and are also a component of many commonly used moisturizers and cosmetics.

Interestingly, each of the study subjects has a KDSR mutation that might have been missed by standard analysis methods. Three of them have a silent substitution that usually would be considered harmless, but this particular mutation was demonstrated by the team to disrupt splicing -- the assembly of gene copies that are translated into proteins.

Additionally, while some subjects had observable mutations in both copies of the gene (one inherited from each parent), two subjects initially seemed to show only one mutation, said Dr. Lynn Boyden of the Yale Department of Genetics. "This led us to look more closely," said Boyden, the lead author on the study.

The researchers noticed that both subjects shared a common benign variation in the KDSR gene. It appeared too frequently in the population to be disease-causing, but too rare to be a coincidental observation, and was a clue that these individuals likely also shared another KDSR mutation, one that contributed to disease but wasn't revealed by exome sequencing.

Sequencing of the entire genome of one of the subjects validated this hypothesis, exposing a large inversion that swapped the beginning of the KDSR gene with an unrelated sequence, and thereby disrupted the gene's expression. Researchers often save money by sequencing only exomes, which are ~1% the size of genomes, but this is an example of the kinds of mutations that can be missed. "This underscores the importance of comprehensively investigating unsolved genetic diseases," Boyden said.

The researchers also found that a commonly used acne medication, isotretinoin (Accutane), counteracts the effect of the mutations, allowing the skin to employ a different biological pathway to produce ceramides and to prevent the skin condition. "In both patients who've utilized it, the medication has cured the disease," Choate said.

In addition to identifying effective treatment of a rare and disfiguring condition with an existing medication, the study results also highlight the central role of ceramides in skin health, and their value as common ingredients in many moisturizers and other cosmetic products, said the researchers.


Materials provided by Yale University. Original written by Ziba Kashef. Note: Content may be edited for style and length.

Disclaimer: DoveMed is not responsible for the accuracy of the adapted version of news releases posted to DoveMed by contributing universities and institutions.

Primary Resource:

Boyden, L. M., Vincent, N. G., Zhou, J., Hu, R., Craiglow, B. G., Bayliss, S. J., ... & Paller, A. S. (2017). Mutations in KDSR Cause Recessive Progressive Symmetric Erythrokeratoderma. The American Journal of Human Genetics100(6), 978-984. DOI: 10.1016/j.ajhg.2017.05.003

Was this article helpful

On the Article

Krish Tangella MD, MBA picture
Approved by

Krish Tangella MD, MBA

Pathology, Medical Editorial Board, DoveMed Team

0 Comments

Please log in to post a comment.

Related Articles

Test Your Knowledge

Asked by users

Related Centers

Loading

Related Specialties

Loading card

Related Physicians

Related Procedures

Related Resources

Join DoveHubs

and connect with fellow professionals

Related Directories

Who we are

At DoveMed, our utmost priority is your well-being. We are an online medical resource dedicated to providing you with accurate and up-to-date information on a wide range of medical topics. But we're more than just an information hub - we genuinely care about your health journey. That's why we offer a variety of products tailored for both healthcare consumers and professionals, because we believe in empowering everyone involved in the care process.
Our mission is to create a user-friendly healthcare technology portal that helps you make better decisions about your overall health and well-being. We understand that navigating the complexities of healthcare can be overwhelming, so we strive to be a reliable and compassionate companion on your path to wellness.
As an impartial and trusted online resource, we connect healthcare seekers, physicians, and hospitals in a marketplace that promotes a higher quality, easy-to-use healthcare experience. You can trust that our content is unbiased and impartial, as it is trusted by physicians, researchers, and university professors around the globe. Importantly, we are not influenced or owned by any pharmaceutical, medical, or media companies. At DoveMed, we are a group of passionate individuals who deeply care about improving health and wellness for people everywhere. Your well-being is at the heart of everything we do.

© 2023 DoveMed. All rights reserved. It is not the intention of DoveMed to provide specific medical advice. DoveMed urges its users to consult a qualified healthcare professional for diagnosis and answers to their personal medical questions. Always call 911 (or your local emergency number) if you have a medical emergency!