Branchio-Oto-Renal Syndrome - The Cain Foundation

Research directions into Branchio-oto-renal syndrome
There are three major objectives:

1. Studies of the distribution of DNA variation (often called mutations) in the known BOR genes. Usually a change in a gene known as EYA1 has the potential to cause BOR. By examining a series of families with BOR, scientist get an excellent idea about the gene and how the gene operates. It also helps clinicians by providing them an exact diagnosis of BOR. We have found out so far that changes in the BOR gene(s) that inactivate the gene at or below 50% of normal are sufficient to cause the disorder. This is important since it gives us an insight into possibilities for treatment and for new avenues of investigation into reasons why some people have a more severe problem than others. It also gives us some very basic information about the gene specifically about what parts of the gene are important. One aspect of this objective is to find what factors influence the severity of BOR symptoms. We observe that some people have very mild symptoms while others, even in the same family, have severe problems like total deafness or a missing kidney. We need to understand why and how this occurs. As the present time, the best thought is that other genes interact with the major BOR genes, but this has not been proven. There may be environmental factors present during pregnancy that are important. Understanding these interaction will help us in counseling families and, most important, in designing ways that might help make the symptoms milder.

2. Discovery of other genes that cause BOR and related problems. Scientists know that there are other genes that cause BOR. Three different genes have so far been discovered. One, called EYA1, is responsible for the majority of cases of BOR. We know that there are other genes based on observations of the inheritance of BOR in certain families that places their BOR gene outside the know locations for the three known genes. These other genes, once we have found them, will give us a better picture about how the different genes operate together to help develop the ear and the kidney.

3. Investigation into how the BOR genes control development. The BOR genes are important for the development of the ear, lower jaw, and kidney. They essentially help to direct the development of these structures. Understanding of how the genes work will provide the information needed in order to some day be able to actually reconstruct these structures. Tissue engineering is the process by which specific organs or body structures might be regrown to correct a mistake caused by a gene that is not functioning properly. For example, the kidney is a complex organ whose growth and development is controlled by large orchestra of genes. We don�t yet fully understand what, or how many, genes are involved. But, scientists are beginning to put together important pieces of the music. Some of the BOR genes are involved since, when they are �knocked out,� a kidney abnormality can sometimes result. It is hoped that someday, damaged kidneys can be corrected by the application of the knowledge derived from our research. This will help not only people with BOR, but people with other kidney disorders as well. The same is true for hearing as well. It may be possible some day to regrow a cochlea and to correct a hearing loss biologically using knowledge gained from your participation in BOR research.

William J. Kimberling, Ph.D.
Professor of Biomedical Sciences and
Director of the Center for the Study and Treatment of Usher Syndrome
Boystown National Research Hospital
Omaha, NE USA.