While most instances of the skin disorder ichthyosis have a known genetic cause, some cases are still unexplained. Using exome and whole genome sequencing, Yale scientists discovered a new mutation and identified a potential new treatment—the acne drug Accutane.
Ichthyosis is a group of disorders characterized by dry, scaly or thickened skin. Mutations in more than 40 genes have been identified as the cause of several types of ichthyosis, according to the National Institute of Arthritis and Musculokeletal and Skin Diseases.
Seeking potential new causes for the disorder, the Yale team sequenced patients’ exomes, the part of the genome that codes for proteins, according to a statement. They found mutations in the gene KDSR that stop the skin from producing ceramides, fat molecules that prevent the skin from losing water. The study is published in the American Journal of Human Genetics.
However, exome sequencing has limits—since the exome makes up only 1.5% of the genome, this method can miss disorder-causing mutations.
The researchers noticed that some patients have mutations in both copies of the KDSR gene, but that two patients seemed only to have one mutation, which “led us to look more closely,” said lead author Lynn Boyden, Ph.D., in the statement. The team then sequenced the genome of one of the patients and found an inversion mutation in the KDSR gene that blocked the gene’s expression.
“This underscores the importance of comprehensively investigating unsolved genetic diseases,” Boyden said. Whole exome sequencing takes less time and costs less than whole genome sequencing, according to the Rare Genomics Institute. And while researchers tend to opt for the quicker, cheaper option, the Yale team’s work highlights mutations that can slip past.
Ichthyosis has no cure—current treatments include topical lotions and creams to control symptoms. Researchers are seeking ways to manipulate genes to treat the disorder, as well as working on new pharmaceutical treatments.
The Yale team discovered that the acne med isotretinoin, or Accutane, targets the effects of the KDSR mutation. The drug lets the skin use an alternate pathway to produce ceramides and prevent ichthyosis.
“In both patients who’ve utilized it, the medication has cured the disease,” said senior author Keith Choate, an associate professor of dermatology at Yale.