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Cellular problem discovered behind syndrome of obesity, learning disabilities

Many a high school biology student has glanced into a microscope to see the planet's smallest animals -- paramecium and the like -- being propelled by the waving, hair-like projections known as cilia. But cilia are also found in human cells, helping move fluid and mucous around in the brain, lung, eye and kidney, or sticking out from cells to act like antennae.

Studying families with a relatively rare condition called Bardet-Biedl syndrome (BBS), characterized by obesity, learning disabilities and eye and kidney problems, the researchers discovered a new gene involved. Furthermore, the gene's protein, BBS8, is found only at the base of cilia, the scientists report in the Sept. 21 advance online section of Nature.

"BBS is a relatively rare genetic disorder, but it has traits common to many people," says Nicholas Katsanis, Ph.D., assistant professor in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins. "We don't know yet how the ciliary defect might lead to obesity or learning disabilities, but the finding provides a new avenue to studying these genetically murky traits.

"It is very difficult to translate genetic understanding into a cellular mechanism that explains what is seen in a disease. But such efforts are what genetic medicine is all about," adds Katsanis.

Some aspects of BBS have been linked to ciliary defects in other conditions. Cilia are known to play key roles in mammalian development, creating what's known as left-right asymmetry so organs like the heart, lungs and liver end up in the right place. In people with BBS, sometimes left-right asymmetry is reversed. Also, malfunctioning cilia in the back of the eye are known to cause retinal dystrophy and eventual blindness, and ciliary problems in the kidney lead to structural problems in the organ.

But even though these primary characteristics of BBS had been tied to ciliary defects, the condition itself and its other traits -- obesity, learning disa
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21-Sep-2003


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