The Genetics of Dystonia- DYT1
Hi -
If you are one of those special cases who does carry the DYT1 gene or a non-carrier, but the disorder runs in your family, consider posting your feelings about this. What does it feel like to have an identified genetic disorder ? Do you feel guilt about passing it on to children ? Do you worry about other gene tests being developed for dystonia ? Has it changed your life in some way ? How so ? Does knowing the cause of dystonia make it easier to deal with symptoms or not ??? have you undergone counseling ?
Share your thoughts , so others can learn about the impact of genetics and dystonia. Not all of us know about this perspective.
beka
If you are one of those special cases who does carry the DYT1 gene or a non-carrier, but the disorder runs in your family, consider posting your feelings about this. What does it feel like to have an identified genetic disorder ? Do you feel guilt about passing it on to children ? Do you worry about other gene tests being developed for dystonia ? Has it changed your life in some way ? How so ? Does knowing the cause of dystonia make it easier to deal with symptoms or not ??? have you undergone counseling ?
Share your thoughts , so others can learn about the impact of genetics and dystonia. Not all of us know about this perspective.
beka
Tags: ashkenazi, brain, counseling, dystonia, dyt1, genetics, heredity, neurology, pedigrees, spasm
Replies to This Discussion
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Permalink Reply by beka on -
Are there really no DYT1 geners out who can explain their feelings about carrying the gene ? I would imagine that guilt would certainly riddle me if I had children. It would eat at my soul constantly.
The DYT1 gene :
The sequence of this DYT1 gene reveals that it codes for a new class of protein called"torsin A". Torsin A is an ATP- binding protein and has high homology to three mammalian genes (human, mouse, and rat torsin A) as well as two other proteins related to Tosin A (torp1 and torp2) and a torsin-related protein in C. elegans (torpCel). The glutamic-acid pair is conserved in all human, rat and mouse torsin A transcripts, suggesting that it is part of a functional domain. Torsin A also has a distant relationship to the heat-shock protein/Clp protease family of proteins (Ozelius, et al, 1997). Heat shock proteins typically contain one or two highly conserved ATP-binding domains and display ATPase activity. These proteins act as thermo "protectors" to other proteins involved in cellular function and metabolism. They protect proteins from temperature fluctuations and help proteins maintain their shape. By maintaining the strength and resiliency of cellular proteins, heat-shock proteins protect cells from deadly environmental, biological, and chemical stress (Schirmer, 1996). The torsin A protein is comparable to two representative members of the heat-shock protein family.
Discovery of the DYT1 gene and its encoded protein, torsin A, will facilitate further understanding of the molecular basis of this crippling disease. This discovery is the first step in being able to design new therapies or treatments for people that suffer from early-onset torsion dystonia. The next task for researchers will be to clarify the function of this 'torsin A' protein. Researchers plan to develop an animal model for early-onset torsion dystonia which "could provide valuable insights into the environmental factors that influence the onset of this disorder" (Ozelius...et al,1997). Interventional therapies may develope to prevent the mutated gene from causing this disorder once these environmental stresses are identified. Understanding the function of the torsin A protein will also provide insight into the developmental patterning of the neuronal complexity of the basal ganglia, whose function is disrupted in other movement disorders such as Parkinson's disease. Thus, this research may also lead to insight into Parkinson's disease. ( So, they have said for years now...)
Source - University of Arizona Biochemistry and Genetics.
All this sounds way too complicated for my medical mind at 1 am in the morning. Also information and reseacrh has somewhat waned when it comes to the DTY1 Torsion protein. I still don't understand its true impact on us.
Those who carry the DYt1 gene make up less than 10 % of the dystonia population. I always ask - some get angry - what about us , the other 90 %, do we not count in research ? I often feel left out of the picture with all the emphasis on the DTY1 gene.
beka
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Permalink Reply by beka on
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Genetic Basics :
Genetics (from Ancient Greek γενετικός genetikos, “genitive” and that from γένεσις genesis, “origin”, a discipline of biology, is the science of heredity and variation in living organisms. The fact that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding. However, the modern science of genetics, which seeks to understand the process of inheritance, only began with the work of Gregor Mendel in the mid-nineteenth century. Although he did not know the physical basis for heredity, Mendel observed that organisms inherit traits in a discrete manner—these basic units of inheritance are now called genes.
Genes correspond to regions within DNA, a molecule composed of a chain of four different types of nucleotides—the sequence of these nucleotides is the genetic information organisms inherit. DNA naturally occurs in a double stranded form, with nucleotides on each strand complementary to each other. Each strand can act as a template for creating a new partner strand—this is the physical method for making copies of genes that can be inherited.
The sequence of nucleotides in a gene is translated by cells to produce a chain of amino acids, creating proteins—the order of amino acids in a protein corresponds to the order of nucleotides in the gene. This is known as the genetic code. The amino acids in a protein determine how it folds into a three-dimensional shape; this structure is, in turn, responsible for the protein's function. Proteins carry out almost all the functions needed for cells to live. A change to the DNA in a gene can change a protein's amino acids, changing its shape and function: this can have a dramatic effect in the cell and on the organism as a whole.
Although genetics plays a large role in the appearance and behavior of organisms, it is the combination of genetics with what an organism experiences that determines the ultimate outcome. For example, while genes play a role in determining a person's height, the nutrition and health that person experiences in childhood also have a large effect.
Although genes contain all the information an organism uses to function, the environment plays an important role in determining the ultimate phenotype—a dichotomy often referred to as "nature vs. nurture." The phenotype of an organism depends on the interaction of genetics with the environment. One example of this is the case of temperature-sensitive mutations. Often, a single amino acid change within the sequence of a protein does not change its behavior and interactions with other molecules, but it does destabilize the structure. In a high temperature environment, where molecules are moving more quickly and hitting each other, this results in the protein losing its structure and failing to function. In a low temperature environment, however, the protein's structure is stable and functions normally. This type of mutation is visible in the coat coloration of Siamese cats, where a mutation in an enzyme responsible for pigment production causes it to destabilize and lose function at high temperatures.The protein remains functional in areas of skin that are colder—legs, ears, tail, and face—and so the cat has dark fur at its extremities.
Environment also plays a dramatic role in effects of the human genetic disease phenylketonuria. The mutation that causes phenylketonuria disrupts the ability of the body to break down the amino acid phenylalanine, causing a toxic build-up of an intermediate molecule that, in turn, causes severe symptoms of progressive mental retardation and seizures. If someone with the phenylketonuria mutation follows a strict diet that avoids this amino acid, however, they remain normal and healthy.
OK, anyone own a Siamese cat with dystonia ?? Talk about complex.
beka
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Permalink Reply by Ellen S on -
Here is what the National Institute of Health says about the genetics. Nice chart etc. CLICK HERE
There is another somewhere. I'll try to find it...
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Permalink Reply by Ellen S on
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Oops, I forgot this would post on top of the other below. Sorry!
Here is a link to the newsletter of the World Federation of Neurology. Down about the middle is a detailed explanation of the different genetics and their specific symptoms and differences. www.wfneurology.org/docs/pdf/wn_sept2005.pdf+%22dopamine+responsive..."">CLICK HERE
Sparky, you're so on the ball, I imagine you've already found these, but thought I'd throw them out there anyway.
The info is a bit heady, but very informative for those curious to the specifics.
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Permalink Reply by beka on
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A question for the Forum - Does genetic research really matter to you today as you manage your dystonia TODAY ??
beka
( Opening a Pandoras' Box !! )
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Permalink Reply by Ellen S on
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Today, yes. It helps to know it's not psychogenic. It's frustrating to know how slow research takes, and I'm resigned to dealing with my symptoms as they happen, but looking forward to a better tomorrow.
When my kids want to have kids, then it will probably really interest me.
Looking forward to seeing what everybody else thinks...
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Permalink Reply by Dianne Rees on -
As Uncle Sparky's pointed out, the genetics of dystonia are complex. There are different types of dystonia, each associated with different genetic risk factors. Even if you have a type of dystonia associated with one type of gene, such as DYT1, a mutation in that gene can be "dormant" (probably because of environmental factors and other genes at play). So knowing that you have a genetic mutation in one dystonia-related gene may not be all that helpful.
That being said, as Ellen noted, by identifying even one risk factor, a physician can make a more informed diagnosis (or at least can consider further tests that are more appropriate). Also, by knowing how suspect gene(s) act in the body, researchers can identify candidate drug targets for clinical trials that may happen sooner than later (ok, potentially in the next decade).
Unfortunately, the only way to make sense of complicated genetics for future generations is to collect large amounts of data from present generations.
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Permalink Reply by Karen on -
Anyone else out there have a mutation--PINK-1? Apparently it is known to be connected to early onset Parkinson's. I have the mutation, but my primary symptoms are dystonic, but I didn't show any of the other dystonia genetic abnormalities. I don't seem to be following any regular progression paths, if there is such a thing. My neurologist is fascinated, and while I am happy to oblige him, it would be nice to not ALWAYS have the freaky illnesses.
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