Medical Update

by Dr. Kathryn Swoboda

As everyone is probably aware from recent news coverage, the human genome project is nearly completed. Regarding AHC specifically, as you probably know by now, we cloned the translocation breakpoint nearly a year ago, and identified a bacterial artificial chromosome (BAC) spanning the breakpoint between chromosomes 3 and 9. Within the last three months, we have been able to completely assemble the genetic sequence in the region of the translocation on chromosome 9, and we now know all the genes in the region. We also have the entire sequence in the region of interest on chromosome 3.

With the help of a fabulous technician in the laboratory who recently relocated from Brigham and Women’s Hospital in Boston, we have been “sequencing” or decoding genes using a panel of a dozen of the sporadic patients from the database. Unfortunately, it has been a bit more difficult to identify the precise translocation breakpoint due to technical issues. Therefore, with the help of Dr. Liharska, a mother of one of the patients with AHC in the database, we have established a collaborative effort with a group in the Netherlands under the direction of Dr. van den Maagdenberg. Congratulations are in order to Dr. Liharska for this excellent suggestion. Their group is helping to do cosmid FISH (fluorescent in situ hybridization) to help us narrow down even further the exact translocation breakpoint. Because cosmids are much smaller than BACs, they contain a much tinier piece of DNA, thus narrowing down the region to a piece of DNA much smaller than a BAC. The bottom line is, we’ve got to be close! Regarding the clinical part of the database, we need to do some more work, but we are making great progress. Catherine McKenna has been working hard to help get all the corresponding medical records and completed questionnaires back on each child, but it has been challenging.

Regarding these questionnaires, We are particularly interested in getting people to answer the questions regarding prior benefits and side effects of medications which may have been tried along the way. We have some preliminary data that another category of medications besides flunarizine may sometimes be helpful in controlling certain symptoms. We realize that it is difficult for families to remember all the details, which is why obtaining the medical records are so vital. I am still hoping to get as much detail regarding the prior metabolic workup in these kids – they went through all that testing, so we may as well try to make some sense of it. Sometimes what doesn’t appear significant in a single child can show up as a pattern when all the data is reviewed. We also hope to establish a photograph database to analyze the children for subtle features that might share in common. We plan to digitize those photos and use computer software to help in our analysis. For this, we would like families to take two photos, one straight on of the head and face, and one lateral view of the face and head only. Send us the copies and we’ll take it from there. These photos will only be used for this purpose, and we have a separate consent form we’d be happy to forward to families.

One final note: We are currently writing an NIH grant for further support on this project.

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