Could seizures, developmental delay, a lack of coordination, and hearing loss be possibly connected? Yes, say Yale researchers, who have found the common thread running through these health conditions - which has been identified as a previously undescribed syndrome.
The researchers have revealed that they made this advance while investigating the genetic causes of blood pressure variation.
AdvertisementThey say that their findings illustrate the power of genetic studies not only to find causes of chronic ailments, but also to identify a common cause in a seemingly unrelated set of symptoms in different parts of the body.
"Our ability to unequivocally and rapidly define new syndromes and their underlying disease genes has progressed dramatically in recent years. A study like this would have taken years in the past, but was accomplished in a few weeks by a single fellow in the lab," said Richard Lifton, chair of the Department of Genetics at the Yale School of Medicine and senior author of the study.
Ute Scholl, a post-doctoral fellow in Lifton's lab, conducted a genetic analysis of 600 patients for causes of salt-handling defects of the kidney, which led to high or low blood pressure.
She identified a group of five patients from four families in Afghanistan, Turkey, Great Britain and Canada who had, in addition to a salt-handling defect, diverse neurologic problems.
The researcher said that the patients had similar clinical features, which suggested that a single defect might be behind them all.
In a matter of weeks, she found that all five had inherited mutations in the gene KCNJ10, a potassium channel that is expressed in the brain, inner ear and kidney.
Scholl highlighted the fact that past experiments on mice had implicated this channel in the brain, but the human findings clearly established its essential role in renal salt handling.
In the brain, the mutation apparently interferes with the ability to clear neurotransmitters and potassium from synapses, leading to seizures. The same channel is required for sound transduction in the inner ear.
The new findings implicated this channel in maintenance of the activity of the sodium pump in the kidney, the major driver of salt reabsorption.
The authors call this new syndrome SeSAME because of the clinical features of seizures, sensorineural deafness, ataxia, mental retardation and electrolyte imbalance.
Lifton hopes that the new findings will prove helpful for doctors in identifying people with the new syndrome, and lead to greater recognition that patients with apparently complicated syndromes may often have simple underlying defects that can be understood.
The study has been published in Proceedings of the National Academy of Sciences.