Cilia Defect Found in Rare Genetic Disorder

Researchers have found that a mutation in the BBS8 gene causes a defective protein to be produced in the cilia of cells in the brain, lung, eyes, and kidneys of patients suffering from the rare genetic disorder Bardet-Biedl syndrome (BBS). BBS is a genetically heterogeneous disorder characterized primarily by retinal dystrophy, obesity, renal malformations, and learning disabilities.

The BBS8 gene was identified by performing gene scans on members of families with members suffering from BBS. In these individuals, defective BBS8 protein was found in ciliated structures, such as the connecting cilium of the retina and columnar epithelial cells in the lung. In cells, BBS8 localized to centrosomes and basal bodies and interacted with PCM1, a protein probably involved in ciliogenesis. Experiments by investigators at Johns Hopkins University (Baltimore, MD, USA; www.jhu.edu) working with the C elegans worm model revealed that the defective protein was expressed exclusively in ciliated neurons, and contained regulatory elements for RFX, a transcription factor that modulates the expression of genes associated with ciliogenesis and intraflagellar transport. These findings were published in the September 21, 2003, online edition of Nature.

"BBS is a relatively rare genetic disorder, but it has traits common to many people,” said senior author Dr. Nicholas Katsanis, assistant professor in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins University. "We do not 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.”




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