Rare disorder offers genetic clues to internal clock

October 21, 1999
Web posted at: 2:03 PM EDT (1803 GMT)

In this story: An unexpected discovery A human clock gene RELATEDS

By Christine Cosgrove

(WebMD) -- Scientists have found an important clue about the location of a gene that regulates the human internal clock, according to data presented Wednesday at the 49th annual meeting of the American Society of Human Genetics in San Francisco.

The researchers said such a gene may somehow control the clock and its regulation of periods of sleep and wakefulness, and adjustment to patterns of sunlight. Also known as the circadian rhythm, the clock is a fundamental characteristic of all living organisms, said researchers, who added that the discovery could lead to a better understanding of sleep disorders, such as jet lag and insomnia.

An unexpected discovery

Scientists only happened upon the gene's approximate location by studying a rare genetic disorder that involved some sleep disturbances in a group of children, said French pediatrician Dr. Helene de Leersnyder, who led the study.

Just over a year ago, de Leersnyder, an expert in sleep disorders, attended a support group meeting of parents whose children suffer from the disorder called Smith-Magenis syndrome. At the meeting, de Leersnyder said she was surprised by the unusual and severe sleep disturbances that the parents described.

"I listened to their story and realized I had 20 parents describing the same thing -- something I'd never heard of," she said.

After monitoring the children over a period of time, she and her colleagues at the Hospital Necker in Paris, discovered that the children's sleep disturbances stemmed from an "inversion of melatonin." By measuring the amount of melatonin in their blood over a 24-hour period, she said that she found that their body "clocks" were completely backward.

In normal children and adults, melatonin levels peak at night and fall during the day, she said. In the children with Smith-Magenis syndrome, just the opposite occurs.

The disorder, which was discovered less than 10 years ago, is caused by a genetic abnormality on chromosome 17 and occurs in one out of 25,000 children, who are characterized by certain physical traits -- tantrums, hyperactivity, mental retardation and severe sleep disturbances, de Leersnyder said.

She added that the discovery of melatonin inversion may point to the reason for some of the aggressiveness and hyperactivity of these children who are severely sleep deprived. Although she does not think it is possible that lack of sleep could cause retardation, the results may open the door to finding new treatments, such as methods for blocking melatonin production during the day and boosting it at night.

A human clock gene

The results of de Leersnyder's study may be another piece in the puzzle for geneticists interested in figuring out how the biological clock works, said Mike Young, a professor of genetics at Rockefeller University in New York, who studies the circadian rhythms of mice and fruit flies.

Geneticists have already found circadian genes in the fruit fly and mouse, Young said. Now, researchers may be one step closer to finding the first circadian gene in humans -- possibly on chromosome 17.

Young said that the study also adds a new wrinkle to the significance of the melatonin rhythm and "suggests that a fundamental change in the way a clock is running may have a very debilitating effect on behavior and development."

RELATEDS AT :

Insomnia
Human gene research

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American Society of Human Genetics
National Sleep Foundation

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