Genetic insights on dermatologic disease

A unique opportunity for cell-based therapeutics.


Keith Choate, MD, PhD, FAAD
Keith Choate, MD, PhD, FAAD

During Sunday’s Plenary, Keith Choate, MD, PhD, FAAD, associate dean for physician-scientist development and professor of dermatology at Yale School of Medicine, who presented the Marion B. Sulzberger, MD Memorial Award and Lectureship, discussed the genetics of ichthyosis and his work identifying new pathways for disease pathogenesis and therapeutic intervention.

“The skin is an extraordinary genetic model containing 85 billion nucleated cells, with three billion new cells generated daily. Yet our genetic understanding of many cutaneous disorders remains unsolved,” Dr. Choate said. For increased understanding, it’s important to get the inside story.

“The use of genetics in dermatology allows us to think about the fundamental mechanism of skin diseases,” Dr. Choate said.

Through genetic research, mutations in 50 genes have been discovered as the cause of ichthyosis, all of which converge on the defective barrier function, leading to scaling and redness. Using genetics to discover the cause of skin disorders, Dr. Choate discussed gene discovery in ichthyosis with confetti (IWC), which manifests as erythroderma at birth with white spots arising early in life that increase in number and size over time.  

IWC is characterized by revertant mosaicism via mitotic recombination. Most patients with IWC demonstrate frameshift mutations in KRT10, Dr. Choate said. IWC mutant KRT10 may increase the rate of mitotic recombination and provide selective advantage to revertant clones.

Spontaneous revertants offer a unique opportunity for cell-based therapeutics without the need for potentially harmful genetic manipulation, Dr. Choate said. “It’s clinical insights like these, using genetic tools, that permit discovery and allow us to move the field forward.”

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