Just as the discovery of penicillin was serendipitous, so too was the new genetic syndrome discovered by two Yale researchers originally investigating abnormal blood pressure.
While studying rare patients with abnormalities in blood pressure, Richard Lifton, chair of the Genetics Department at the Yale School of Medicine, and Ute Scholl, a genetics post-doctoral associate, discovered a new genetic disease that can be characterized by a myriad of seemingly unrelated symptoms.
While researching abnormalities in blood pressure, Scholl made a small observation — one unrelated to the study at hand — that led to a large discovery.
“I was looking through five of the patients we were studying and realized that they all had similar symptoms, such as seizures at a very early age, coordination problems, loss of hearing and mental retardation,” Scholl said. “I thought it was remarkable, so I asked Dr. Lifton about it, and we thought it might be a entirely new syndrome.”
Scholl noted that two out of the five patients who showed this cocktail of symptoms were related and that two of the patients’ families had siblings with similar symptoms. Both these clues pointed to a genetic disease, she said.
By using a new DNA-sequencing technique, Scholl and Lifton were able to narrow down the location of the candidate gene within the human genome. They then surveyed several candidate genes they had thought might underlie the syndrome and discovered that one of the genes had a mutation in all five patients.
“It was an amazingly good idea and only took an amazingly short period of time to get to the identification of the gene,” Lifton said. “This is a project that years ago would have taken a very long time, and here it took an astoundingly short period of time.”
The gene, KCNJ10, is a potassium channel that is expressed in the brain, inner ear and kidney, according to the March 16 issue of the Proceedings of the National Academy of Sciences, where their findings were published.
“The finding demonstrates the essential role of the particular potassium channel for regulating brain activity, the function of the cochlea in the ear and salt reabsorption in the kidney,” Lifton said.
The scientists named the new syndrome SeSAME, an acronym for its clinical features: seizures, sensory neural deafness, ataxia, mental retardation and electrolyte imbalance.
The discovery may also shed light on seizure disorders. Lifton noted that despite the widespread prevalence of seizure disorders, scientists remain in the dark about their underlying causes.
The researchers are now concentrating on the mechanism through which the mutation exerts its influence and causes the various symptoms. They also plan to observe more patients to develop a more comprehensive characterization of the syndrome.
Lifton said the finding demonstrates the power of observation — which, in Scholl’s case, led to unexpected results.
“I think this story highlights the importance of astute clinical observation,” Lifton said. “It would have been very easy to say that this patient has too many medical problems to figure out an underlying cause, but we were able to say that all of those problems were explained by a single gene.”