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Proteus Syndrome: B-Roll Video Footage and Video Sound Bites

July 14, 2011
Leslie Biesecker, M.D.



Below are clips containing high-definition video footage of Proteus syndrome, the Proteus Syndrome Telebriefing and an interview with Leslie G. Biesecker, M.D., Chief and Senior Investigator in the Genetic Disease Research Branch of the National Human Genome Research Institute at the National Institutes of Health, Bethesda, Maryland, on July 14, 2011. Dr. Biesecker led a team of researchers that discovered the mutation that causes Proteus Syndrome, as reported in The New England Journal of Medicine.

The National Human Genome Research Institute provides this interview to assist reporters and producers interested in covering this discovery and to help the public understand the work of the institute.

Video Footage

Video Sound Bites

Sound Bites by Leslie Biesecker, M.D.
Chief and Senior Investigator,
Genetic Disease Research Branch, NHGRI
Bethesda, Maryland
Clip # Running Time Quotes (Text) Web Preview* For Broadcast**
1 30 seconds

I'm Les Biesecker. I'm a medical geneticist, senior investigator in the Genome Research Institute. My job being to figure out the molecular cause of disorders that affect children and adults, especially those that are inherited birth defects and other kinds of conditions. So we do both clinical research and molecular research.

(3.20 MB)
(47.64 MB)
2 32 seconds

And so what Proteus syndrome is is parts of the body - you completely lose control of that regulatory growth - that regulated growth, and they grow much, much faster and in an uncoordinated fashion, either compared to the other limb, right versus left, or sometimes even within a single limb, a small part of that limb can grow out of proportion to the other parts.

(3.79 MB)
(56.32 MB)
3 28 seconds

It's a devastating disorder, where patients - parts of patients' bodies grow out of control, and it has a high frequency of early mortality. So it is imperative that we find the cause for this disorder and figure out how to convert knowledge of that cause into an effective treatment. And the wonderful thing about this finding is that this is a pathway and a gene and a mutation that we know a lot about.

(3.91 MB)
(58.01 MB)
4 31 seconds

And it's already a target of drug development because it is mutated in certain cancers. So we can piggyback off of the progress that's being made in this mutation in cancer, and try to apply that to patients with disease and this has allowed us to leap hugely forward in our understanding of the disorder and move toward a treatment that a few weeks ago, we had no idea how to tackle. So for the patients with the disorder, it's a huge advance.

(3.96 MB)
(58.77 MB)
5 33 seconds

And most - and second, that people who have the condition have never been known to have effected offspring, and that we know of at least several - at least two pairs - of identical twins, monozygotic twins is the term, the technical term that we would use, who should have the same genomes. One of them has Proteus syndrome, and the other one doesn't. So that tells you that genetically, there's something very different about Proteus.

(4.28 MB)
(63.47 MB)
6 19 seconds So, we've been working on Proteus syndrome for 15 years. And we,ve been trying to crack this problem, using the most recent available technology that was available throughout that 15-year period. And technology has changed a lot in 15 years. Biesecker_06_low.mp4
(2.48 MB)
(36.99 MB)
7 36 seconds And so we assume as next generation sequencing became available, we, together with the Proteus Syndrome Foundation, put together the resources to start whole genome or whole exome sequencing in Proteus syndrome patients, and the trick is, is that instead of comparing patients with the disease to patients without the disease, what we did is we compared the affected parts of the patient to the unaffected parts of the patient. Because if the patient is a mosaic, the mutation should be different in those two tissues, with and without. Biesecker_07_low.mp4
(4.63 MB)
(68.82 MB)
8 36 seconds

So the variation that we found in patients with Proteus syndrome is in a gene called AKT1, which is a gene that is an important part of a - it encodes for a protein that is an important part of a signaling pathway that is important in transmitting signals from growth factors through growth factor receptors into cells to turn cells on, turn cells off, turn genes on, turn genes off, make cells replicate, or regulate cell death.

(4.67 MB)
(69.48 MB)
9 16 seconds

So it's a very specific mutation that we found in patients of Proteus syndrome. In fact, so far, 27 out of 29 patients who have the mutation, all 27 of those patients have exactly the same mutation.

(2.06 MB)
(30.89 MB)
10 25 seconds So in fact, the gene that is mutated in patients with Proteus syndrome was previously characterized exactly because it is mutated in a few percent of a number of human cancers. And those include cancers like breast cancer. About three or four percent of breast cancers have the exact same mutation in them that the patients with Proteus have. Biesecker_10_low.mp4
(3.22 MB)
(47.92 MB)
11 19 seconds

So it's extremely hard to know exactly what the frequency of a disease like Proteus syndrome is. It's - we know it's very, very rare. It's - there's probably fewer than a couple of hundred patients in the United States that have this disorder.

(2.46 MB)
(36.69 MB)
12 10 seconds So the one thing that we know about Proteus syndrome is that it never recurs, has never been seen in more than one individual in a single family. Biesecker_12_low.mp4
(1.38 MB)
(20.42 MB)
13 15 seconds Number one, so far, all the patients have exactly the same mutation, which means that there's only one change, one particular change in one base pair of the genome that could cause this disorder. Biesecker_13_low.mp4
(1.99 MB
(29.44 MB)
14 24 seconds So I think Proteus syndrome is a good example of why we should study rare disease, because this has allowed us to take a very rare disorder, which is - is a supremely important to understand for the patients who have it. But for the patients who don't have it, they should care about this, because this means that we can begin to think about a new class of genetic disease. Biesecker_14_low.mp4
(3.10 MB)
(46.29 MB)
15 20 seconds So the discovery of this AKT1 mutation in Proteus syndrome gives us a very clear pathway towards developing the clinical trials to test agents to control the disease. It will be extremely challenging, and I don't want to pretend that it's going to be simple or fast. Biesecker_15_low.mp4
(2.63 MB)
(38.88 MB)

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Video Specifications

These high-definition videos were shot on a Sony EX-3 and edited at full resolution in an Avid Media Composer. The video clips were exported as MP4 Movies, using the H.264 codec, with the following specifications:

  1. Full raster, 1920 x 1080 pixels frame size
  2. 29.96 frames per second (drop frame)
  3. AAC Stereo, 48 kHz
  4. Data Rate: 15.20 mbits/sec

Terms of Use

These clips were developed for use by broadcast media to assist with the preparation of news stories. All government-produced video is in the public domain and copyright free. Anyone is freely able to use these clips. These clips were created by Genome Productions, a part of the Communications and Public Liaison Branch of the National Human Genome Research Institute. As a courtesy, it is requested that an appropriate acknowledgement be given: "Courtesy: National Human Genome Research Institute."

Last updated: May 30, 2014