米国マルファン症候群患者団体The Marfan Foundationからの情報を中心に、マルファン症候群や関連疾患についての海外情報を翻訳して発信します。


What’s in Your LDS Family Tree? Genetics, Variability, Outcomes (September 1, 2020)




So someone is asking your thoughts again on the variability within one type of Loeys-Dietz-like syndrome if you think it's more likely to be caused by the kind of gene variant, other genetic factors, other external factors-like. What are your thoughts on the variability and the causes of variability?




Yeah, so as we've discussed the, the gene that's involved contributes to variability. As we've discussed the precise mutation that's present influences disease severity and therefore variability between families but as we've also discussed there can be dramatic variation among individuals in the same family with the same underlying Loeys-Dietz syndrome mutation, so therefore, there in that circumstance, we can't blame it on the gene of the variation. We can't blame it on the mutation. All those people have the same mutation. 




So we have to start thinking about other variables, other factors and when we think about those other so-called modifier factors there are two broad classes: one of them is the environment, you know, what has been the experience of that person over time ―― "Did they do a lot of weight lifting early in life" and also "get into a couple of car accidents" and "have high blood pressure that was poorly controlled," whereas their more mildly affected relatives always took meticulous good care of themselves and, you know, didn't partake in any of those risky behaviors. 




We think about medication use, "Did one person start medication at a young age to try to modify the rate of aortic growth?" and another person "Either never took medication or wasn't very compliant with taking their medication when they were supposed to?" So there's a whole big list of potential environmental modifiers that we think about.




But now there's another category of a lot of interest to many researchers and that's something that we call genetic modification. So we talked about we all have 20,000 genes we talked about we, that we all have variation in all those genes and most that variation is innocent ―― it dictates what we look like, what our hair color is, what our eye color is. Sometimes that background normal variation can either make a disease worse, something that we call protected, and I'm sorry aggravating modification, or can make an underlying genetic disease better something that we call protective modification. 




You know, those, as those normal variants pass throughout a family. It's like dealing a hand of cards, you know, is this person with Marfan syndrome, for example, or Loeys-Dietz syndrome going to get a good hand of those normal variants from their relatives just by chance or are they going to get a bad hand or are they going to get dealt the variance in those other genes that make things worse or, or simply fail to protect.




So there's a lot of research now to try to understand those modifiers to understand especially how the protective genes and variants work because if we could understand how nature has learned to protect some people with Loeys-Dietz syndrome perhaps we can use a medication to try to mimic that protective effect to try to duplicate it in someone that did not get dealt the favorable hand of variance.




So I think that it's a combination of what genes involved, what variants involved but also what our life's experiences are and the protective variation that we inherited from from our parents. 




The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.

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