Dr. Keith Choate from Yale just wrapped up his presentation at the #FIRSTNFC First Family Conference in Indianapolis. Dr. Choate gave the conference attendees a update about the amazing progress he and his team at Yale have made on the Gene Discovery Project.
Dr. Choate mentioned that they started doing gene discovery at FIRST family conferences literally in a coat closet at the 2010 conference in Orlando, Florida. And since then, they’ve grown by leaps and bounds. Including the 35 families recruited here in Indianapolis, they’ve recruited 375 total families.
So far, they’ve been able to get a genetic diagnosis for 247 of those families. And since the Denver conference in 2012, they’ve identified three new genes which cause ichthyosis.
Part of the story of the Gene Discovery Project is the story of how advances in genetic sequencing technology has made genetic diagnoses faster and cheaper. Of the 247 families who were able to obtain a genetic diagnosis from Dr. Choate and his team, 70% of them were able to get that diagnosis through their “pre-screening” process, which looks at the 11 most common genes that cause ichthyosis. This “pre-screening” test now costs the Yale lab between $30 and $50 dollars, which is a huge drop in costs from a decade or so ago.
(The remaining 30% of the diagnoses were obtained through the fuller exome sequencing technique.)
Unfortunately, these diagnoses aren’t CLIA-certified, so patients still need to obtain a confirmation of the diagnosis from a CLIA-certified lab like GeneDX. Dr. Choate mentioned that while insurance doesn’t cover that confirmation at first, it can be covered in part when the insurers are informed about the significantly lower cost when compared to traditional testing methods.
The work that Dr. Choate and his team are doing is important because this kind of research is teaching the scientists so much about ichthyosis. Learning more about the specific genetic causes of ichtyosis will enable future research to develop effective therapeutic pathways for treating ichthyosis.
Dr. Choate explained to the audience, “I believe that genetic information is going to become relevant to your therapy.”
For instance, Dr. Choate observed that of the patients who had a diagnosis of epidermolytic ichthoysis, about 75% had KRT10 mutations correlated with gradations in the severity of their symptoms. About 14% had KRT1 mutation and the remainder had KRT2 mutation
Likewise, the ABCA12 gene was previously commonly thought to be solely the cause of Harlequin ichthyosis, the most severe form of autosomal recessive congenital ichthyosis (ARCI). But we now recognize that milder mutations in ABCA12 can cause what we call CIE. Dr. Choate explained, “I think that we’re going to move from definitions of ichthysois from the old terms, to inheritance-based terms.”
Learning about the research that’s going on is very exciting. Dr. Choate’s hope is that everyone in the ichthoysis community will be able to obtain a genetic diagnosis. And that genetic diagnosis will lay the foundation for developing effective therapies in the future. The future is bright!