Rubinstein-Taybi Syndrome: Genetics | Cincinnati Children's скачать в хорошем качестве

Rubinstein-Taybi Syndrome: Genetics | Cincinnati Children's

Rubinstein-Taybi Syndrome: Genetics Bill Mann, Sophia’s dad: "We got a preliminary diagnosis very early, day one in the NICU. And then within a couple of months we actually had empirical evidence that said, 'Yep, this is what you have, there’s no question.'" Elizabeth Schorry, MD, Division of Human Genetics: "Of course, we’re involved at the beginning when they’re first diagnosed. But we also are involved in monitoring children who have RTS, following them, following their development in their medical course. So, I will usually see young children with RTS at least every 6 months until they’re at least 3 years old. And if things are going well I may see them once a year after that." At Cincinnati Children’s, geneticists are an integral part in the comprehensive care of children with Rubinstein-Taybi Syndrome, a rare genetic condition affecting about one in 125,000 people. Those with RTS may have varying intellectual delays as well as distinctive physical features. Dr. Schorry: "Down-slanting eyes or down-slanting palpebral fissures, a beaked bridge to the nose, thin lips and broad thumbs and great toes." (natural sound) Jamie Jackson, Mia’s dad: "Mary is actually the one that diagnosed Mia. Googling all the different symptoms that Mia was exhibiting, we called Children’s and got in and did the genetic test, and she was right." Dr. Schorry: "There are actually two different genes that can cause RTS. The first one is called CREBBP or the CREB-binding protein gene. It’s located on chromosome 16, and it causes the majority of cases of RTS. The second gene is a less common gene, it’s called EP300. And that gene is on chromosome 22, so it’s in a totally different location from the CREBBP gene but can cause the same kind of features of Rubinstein-Taybi Syndrome. There are several different laboratories that testing can be sent to. And they do sequencing of the genes as well as look for deletion and duplication. And the testing is not 100%, there’s still limitations to the testing that we have now. In this diagram the black line here is the DNA, the gray oval shapes are histone proteins, and this area here is the complex that’s formed by the binding of the two different RTS proteins the CREBBP and the EP300. And they then bind to the histones in the DNA and affect whether the DNA is going to be transcribed into creating another protein. As they do this, they actually are regulating the transcription of many, many different genes. So probably hundreds of different genes are turned on and turned off by this complex that’s formed by these two different proteins. So I think it’s really a fascinating way that we’ve learned that the genetics of a single gene can actually affect many different genes. And that’s probably one of the reasons why RTS has so many different physical features and physical effects from one gene." Jessica Froman, Jett’s mom: "When I was in the hospital with Jett, when they first gave him to me, I immediately knew something wasn’t right. They took lots of pictures and blood and all this stuff trying to figure out exactly what it was. He said, 'I’m almost 99.9% sure I know what he has.'" Dr. Schorry: "The majority of the time, the testing is just going to confirm the diagnosis. Like in maybe 10% of the cases, it can give you an idea whether this might be a milder or more severe situation. I believe in complete honesty with families, to let them know what you know and what you don’t know. I don’t encourage them to get on the internet and read everything that’s out there about a particular syndrome because one person’s blog may not be what reality is." Froman: "He’s totally out estimated what they’ve said he’s going to do. Of course, I think his determination and my determination behind him has made it to where’s he’s done that because he’s been in therapy since he was 3 months old." Dr. Schorry: "The syndrome is so variable that we can’t predict, even once we have the genetic testing. You can't predict how mildly or severely an individual child is going to be affected. We’re just going to have to wait and let them show us what they’re able to do."