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Some questions to the groups of Geneticists who are working on Joubert Syndrome answers from the university of Washington
Dr. Philip chance, MD offices by Melissa Parisi, md, PhD

Oct 9, 2003

Hi Everyone:

In response to some questions that some members had regarding the scientists, collaboration and a recent new publications for another mutation being discovered, I sent some questions to the 2 groups of Geneticists that are working on Joubert Syndrome. The responses below are from the Seattle group. I want to make mention that the University if Washington group in Seattle responded very quickly and promptly to my request for answers to these questions.

Cheryl Duquette, President and Co-Founder
Joubert Syndrome Foundation & Related Cerebellar Disorders
6931 South Carlinda Ave.
Columbia, MD 21046
410-997-8084 fax: 410-992-9184
email: joubertduquette@comcast.net

Joubert Syndrome Foundation (JSF) Question: What does the University of Washington research group (headed by Dr. Philip Chance) think of the recent publications in the American Journal of Human Genetics?

Melissa Parisi MD., PhD (MP) Answer: We assume you are referring to the recent publication by 2 separate research groups, one of which was headed by Dr. Joe Gleeson at the University of California in San Diego, and the other of which was by an Italian group. These publications announced the identification of a second locus for a Joubert gene on chromosome 11. This is a very interesting and potentially very exciting development, and we hope that this will lead to new insights into the genetic causes of Joubert Syndrome.

We would like to point out that this new "locus" (or genetic location) for Joubert syndrome represents a large region of genetic material (millions of base pairs of genetic information) and that the specific disease-associated gene has not yet been identified. In fact, there may be several hundred different genes within this locus on chromosome 11. The task of identifying a specific gene may take years. The first locus identified for Joubert syndrome on chromosome 9 was first published in 1999, and the gene has not yet been found. Unfortunately, the pace of progress in genetic research is sometimes slower than we would like. And even when a gene is discovered, it does not always lead directly to a treatment or a cure for the condition.

Since the publication of the chromosome 11 locus, we have examined markers in this region in samples from many of our families, and our data suggest that the majority of families are not likely to be linked to this region. This implies that the Joubert gene in most of the families that we have under study from the U.S. is not located on chromosome 11. Previous studies in our laboratory have also excluded the chromosome 9 locus in the majority of our families. Nevertheless, we will continue to examine chromosome 11 and other chromosome regions in order to find Joubert genes. We anticipate that there are likely to be many genes for Joubert syndrome (perhaps 5-10). Therefore, this finding should spur increased efforts to find ALL of the genetic causes of Joubert syndrome, but does not provide the final answer to our quest.

JSF Question: Are the University of Washington team and Dr. Joe Gleeson’s group working together or separately on the genetic studies?

We have worked with Dr. Gleeson's laboratory on genetic studies of Joubert syndrome in the past, and we have shared approximately 50 patient samples with his research group. It has always been our goal to pursue this research jointly, but it has been difficult to develop collaborative agreements. In the spring of this year, our group developed a very specific collaborative agreement which was presented to a group of interested laboratories, including Dr. Gleeson's group. Unfortunately, this agreement was ultimately rejected.

We have continued to work with many researchers in the Joubert syndrome field, including Dr. Dobyns, Dr. Maria, Dr. Koenig, Drs. Andermann, and Dr. Dostal. We welcome collaborations and we believe that a combined effort will be most beneficial for success in future projects.

JSF Question: If we have previously sent blood to Dr. Chance’s group at the University of Washington, may we also want to send to Dr. Gleeson’s group in San Diego?

MP Answer: Families are always welcome to send blood to whomever they choose. However, the policy at the University of Washington has been to recommend sampling an individual only once, with the assumption that those samples are precious and should be shared appropriately. We believe that establishing permanent cell lines on each sample we receive is the best way to ensure that there is enough material for distribution among collaborators, so that there is no need to resample children (or adults) if the initial DNA sample runs out. We have been constructing cell lines since we began this research in the early 1990's, and although it is a more expensive and labor-intensive process, we believe the samples deserve this level of commitment.

We would like to remind families that progress in medical research is measured in slow, incremental, and sustained efforts. It is very common for contributions to be made by other researchers who may have been fortunate to find a large, inbred family to study. However, we would caution families that it is not necessary or useful to send blood to every lab that publishes a research paper on Joubert syndrome. Once a gene location is published, other researchers in the field can also work on that region. A discovery such as the chromosome 11 locus is just the
first step in the difficult task of finding the gene, a task which is often shared by many research groups. Our group is committed to the efforts to find Joubert genes, and has been collecting samples for over ten years. We are in this for the long-haul and will diligently follow-up on all discoveries in the Joubert research field, whether they are made by our group or by other groups.

As we stated earlier, we believe that collaborations between laboratories and sharing samples is a very desirable goal. We have reciprocally shared samples in the past with Dr. Gleeson, and with other laboratories. Unfortunately, collaboration between our group and the Gleeson group is limited at this time, and will remain limited until we are able to resolve some serious issues. We hope that this will be rectified in the future.

Families should not be overly discouraged to learn that all of the laboratories are not necessarily collaborating with each other, because it is clear that progress is being made, and we expect the pace of discovery to accelerate. The fact is, competition is usually good for stimulating research activity and new discoveries.

We want to reassure families that when each gene for Joubert syndrome is found, we will look for mutations in the patient samples we have collected. In all likelihood, there will be several different research groups who discover Joubert genes, and we intend to be one of them.

We appreciate the faith that families have placed in our efforts to find Joubert genes and learn more about this condition, and we look forward to continuing our work with the families and the Joubert Syndrome Foundation. We are committed to the mission of the JSF and want to help make discoveries that will have a positive impact on children with this condition. Together we can get the work done!

Thank you for allowing us to answer your questions. Further information on our research is available at our website: http://joubertsyndrome.washington.edu.

Please contact Melissa Parisi MD., PhD if you have additional questions (mparisi@u.washington.edu).

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