"It's becoming very clear that microtubules are so fundamental to cells that if you hit the system with a genetic mutation you will get a disease," says Katsanis. "It's likely that some genes implicated in other multisystem disorders may compromise microtubules' functions, especially in diseases whose physical characteristics overlap with those of BBS."

Microtubules act as the roads that chromosomes travel in order to move to opposite sides of the cell during cell division. They also transport molecules and packets of molecules to the cell membrane for release from the cell, and are the primary skeleton in cellular structures called cilia. BBS4 mutations are likely to affect different microtubule functions in different cell types, including the transport of proteins up and down cilia, Katsanis says.

"In our in vitro systems, if BBS4 didn't work, all the cells died because of microtubule failure," says Katsanis. "It's very likely that in engineered mice, we also may see slower growth, less cell division, and other mutation-induced changes that will explain the condition's various effects. Cell death won't be the only problem."

The Johns Hopkins researchers were funded by the National Institute of Child Health and Development and the March of Dimes. Authors on the report are Katsanis, Jose Badano, Carmen Leitch and Stephen Ansley of the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins; Jun Chul Kim, Muneer Esmail and Michel Leroux of Simon Fraser University, Canada; Sonja Sibold, Josephine Hill, Bethan Hoskins, Alison Ross and Philip Beales, University College London; and Kerrie Venner, Institute of Neurology, London.