As Jewish physician was dying, he recruited a successor to continue his work

Dr. Alan Permutt, who died in 2012, was researching a cure for a rare genetic disorder. 

By Eric Berger, Associate Editor

Dr. Alan Permutt did not live long enough to find a cure for a disease that ailed him, but his successor at Washington University recently moved closer to the finish line. 

Permutt, who belonged to Central Reform Congregation and died in 2012 at age 72, was a leading diabetes researcher, while also being afflicted with the disease. (He died from cancer, not diabetes.)

In the years immediately preceding his death, his particular interest was in a type of diabetes caused by a rare genetic disorder known as Wolfram syndrome.

“He couldn’t finish it, so I took it over,” said Dr. Fumihiko Urano, a Wash U physician and researcher.

Urano is now studying a mild form of Wolfram syndrome caused by a genetic mutation, WFS1 R558C, that is more prevalent among Ashkenazi Jews than in the general population. Urano is simultaneously working on both a way to prevent people from passing the gene to their offspring — or at least to counsel them about its threat — while also trying to cure people already afflicted with the form of the syndrome that can cause diabetes and loss of vision and deafness, among other ailments. 

Urano was working in Boston at the University of Massachusetts Medical School in 2011, and considering moving back to Japan, when Permutt, who was dying of cancer and had collaborated with Urano, reached out about carrying on his research in St. Louis. 

“I was really moved by Dr. Permutt’s enthusiasm about this disease, so I decided to move from Boston to St. Louis,” said Urano. 

A couple years ago, Dor Yeshorim, a New York-based nonprofit that aims to halt genetic disorders prevalent among Jews, contacted Urano and told him about Jewish patients from families with a strong history of diabetes. The organization found that the family shared a genetic mutation, but they could not find the particular gene variant in its database.

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Urano discovered that one in 30 Ashkenazi Jews in New York and Israel had the variant that caused a mild form of the Wolfram syndrome. If two people with this variant procreate, their offspring has a 25% chance of becoming afflicted with the mild form of Wolfram syndrome. (The life expectancy for the more serious and rare form of the syndrome is 30 to 40 years.)

Urano and Dor Yeshorim would like to see widespread genetic testing among Ashkenazi Jews for the variant. Even if a couple both carried the genetic variation, Urano said the doctors could use in vitro fertilization to implant fertilized eggs that do not carry the genetic variation.

“I think it’s good for Jewish people to know if they are carriers of the WFS1 R558C variant — they should at least know, then we could counsel them,” said Urano. 

For those already afflicted with the syndrome, Urano and other researchers are now also studying potential treatments for the mild form of Wolfram syndrome — which Urano thinks could also be used to treat the rarer form. But the researchers must first demonstrate the impact on the larger population because Wolfram syndrome is so rare that it is hard to interest pharmaceutical companies, Urano said. 

In the meantime, Urano also has a particular interest in helping Ashkenazi Jews who face the unique threat of the Wolfram syndrome variant.

Not only were he and Permutt close, but “all of my English teachers and all my clinical and research mentors were Jewish. Even when I was in Japan, my English teacher was Jewish,” Urano said. “I want to help people who helped me.”