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OT: Time for explanations

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  • OT: Time for explanations

    I'm back, sort of. I still have a great deal of work to do but I should explain my absence.

    When I disappeared it was because I made an important discovery regarding my medical conditions and it was absolutely imperative that I research it thoroughly as quickly as possible to verify and document it. I have the final hearing on my disability claim coming up at the end of January and what I found nails my claim totally. I have been spending nearly every waking moment working on this and it is 100% correct. I am sorry for forgetting about a couple of people that I promised to send items to and will rectify that asap. When I get into something like this I forget everything else.

    I have a wide variety of things wrong with my body and have been seeing many doctors for the last 30 years trying to find out what is wrong. It is only in the last couple of years that actual diagnoses have been forthcoming. However, none of the diagnoses go any deeper than simply verifying that the symptoms are real and represent some real medical problem. No doctor has been able to tell me the causes. That makes it impossible to determine what to expect in the future or what might be available in the way of root cause treatment.

    What set me on this investigative track is my recent stroke. I learned sometime after that my cousin who owns a ranch in Montana also had a nearly identical stroke at nearly the same time. Cousin Pete is my age and we have always been good friends. He is a retired cop who worked for the feds and the state of CA and is now retired on disability. We started comparing notes and there are enough similarities in our medical conditions that I became very suspicious that there must be a genetic connection. I have been convinced of that for a long time but this information gave me a place to start looking.

    The single key information is that we both have the same visible evidence of a genetic mutation. As children we both had one unusual feature, a patch of hair that was nearly platinum blonde. That hair eventually fell out fairly early, about age 30. When I looked it up I expected to find it was reasonably common. It isn't. No matter how hard I looked on line I was only able to find a single image of another person with the same type of hair colour. That really jacked up my WTF sensor.

    I shortly found it was related to a gene in mice called "Piebald Lethal". The word lethal really got my attention. Then I discovered that humans have the same genetic feature and it is called Piebaldism. I also discovered that it only appears in about 1 in 400,000 live births. You are born with it and it doesn't change except for falling out. The reason it is so rare is the mutation is usually lethal to the foetus.

    It looks like this:



    When I started looking into it I opened Pandoras's Box. In it I found every single one of my symptoms including ones that I had entirely forgotten or never even considered as in any way related to my current issues.

    Every single one of my numerous medical issues save one are explained completely down to the tiniest detail by a series of related genetic mutations on one copy of Chromosome 4 that I inherited from my mother and the Danish side of the family. It includes my stroke, LO-CCHS (Central sleep apnea), Narcolepsy, Postural Orthostatic Tachycardia, Postural Hypotension, Carotid Sinus Hypersensitivty, Atrial Fibrillation, Polycythemia, Elevated Free Light Chains and other immune issues, fibromyalgia, coeliac disease as well as a number of other issues such as bad teeth and hypersensitivity to bright light. The one that isn't explained is due to a distant past infection and doesn't require explanation.

    I even discovered a probable reason that I am still alive, which I definitely should not be. I have an especially mild form of the sleep apnea that doesn't kill you before age 20. There are about 50 known cases in the world.

    It is all genetic, it's all directly related to Piebaldism and it's all on one copy of chromosome 4. My Aspergers is most likely on the other copy from my father.

    I have always been interested in genetics so I had a leg up on the search. I knew what I was looking for. I found it, in spades. Genetic defects are often clustered near the ends of genes or the segment boundaries. That is what nails this to the ground.

    This map shows the 4 most important mutated genes that are responsible for the majority of the serious problems I have.



    Just those four genes are the cause of 90% of my problems. There are several more that code for things like tooth enamel that are nearby but they aren't relevant to my real problems. Coeliac disease is on there as well. It's even known as "Scandinavian type".

    This is absolutely amazing. Not only does it explain everything it isn't a conjecture. The Piebald mutation is completely diagnostic by the blonde patch and the rest follows as is documented by studies. What has not been documented is anyone living to my age (and my cousin) with this set of problems. Piebaldism doesn't always kill people but the commonly associated LO-CCHS does. That stands for Low (lethality) Chronic Congenital Hypoventilation Syndrome. It has only been documented so far in somebody as old as about 50 in the last couple of years. In fact, I could not have figured this out even just a few years ago. The Human Genome Project is turning the medical world upside down and it is impossible to overemphasize just how significant this new knowledge is to medicine.

    I am currently working on what amounts to a Paper/Case Report and together with my doctor it may be published. He was already planning to publish a case report but has been waiting to see what more could be found out about my condition. He is blown away by what I found. So am I.

    I still have a lot more work to do in documenting this so you may not see much of me here for some time.

    If anybody reading this has a similar type of hair colouration you should visit your doctor for some checks even if you feel perfectly well. The mutation greatly raises the risk for certain type of cancer, especially multiple myeloma which is what my grandfather died from. He of course had the same mutation. It is autosomal dominant which means you only need one copy and if you have that copy it is operational. However, my grandfather managed to live into his 80's before it killed him. That may be due to the other thing I found. On the same chromosome 4 there is a gene that when mutated codes for exceptional longevity. It has an unknown protective effect. Not all mutations are bad but this one doesn't make much difference to the gene pool. Exceptional longevity runs on both sides of my family so I may have a chance to at least make it to 70.

    The best news about all this is that my children did not inherit it and so then neither did my grandchildren. I have been looking for this for around 30 years and I finally have the answer. It is a very strange feeling.
    Last edited by Evan; 11-02-2012, 01:29 PM.
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  • #2
    Well done.

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    • #3
      Good job. Glad your back!

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      • #4
        Interesting sleuthing, Evan. I have several things in common with slight modification - I had white hair as a kid but it turned darker in my 20's. I had a dark patch of hair, very small, that I could never see but my mother spent a lot of time trying to scrub it out. My father was born in Denmark. I have central apnea (an obvious fact to me but which sleep studies fail to identify. With central apnea you stop breathing - no obstructions are involved. I don't even have to be asleep to experience it.). If I have other similar symptoms I'm not aware of them, but I'm now curious. How did you go about having your DNA examined?

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        • #5
          From what you have written, I guess the good thing is its sounds like you will now not have trouble "establishing" what is actually going on or has happened with you as far as the medical community is concerned.
          From my own experiences it is hard not to give up trying to prove something, like a medical condition (never really sure what to call it when there is seemingly no cause) when you are outside that community. There is no one that can know their own body better than themselves and compared to years ago, the internet access can be tremendously helpful BUT trying to convince others can be insurmountable esp when similar symptoms can go in opposite directions vis a vis treatment, if there even is a "treatment".
          Knowing, as you now do, will help tremendously, esp the mindset. Plus that last line is no small bit of importance. I can't imagine how it feels.

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          • #6
            Determination is the number one predictor of success.

            I see a lot of determination on on Evan's part.

            It is satisfying to have a definitive diagnosis after all this time.

            doug

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            • #7
              How did you go about having your DNA examined?
              I haven't. The piedaldism is definitive, especially since we can trace it back photographically through 4 generations. There are only a few syndromes that cause that sort of white hair patch. Piebaldism usually has associated melanin free skin patches but not always. Vitilligo always does and progressive, piebaldism is never progressive with a single isolated exception traced to another gene. Waardenberg Syndrome is similar but always is accompanied by some degree of deafness and/or eyes of two different colours, usually green and blue. We had a cat with that defect, he was stone deaf and a one blue and one green eye. Also, the facial structure is affected with eyes far apart.

              The only thing left is piebaldism. It is absolutely diagnostic. The matchup between known associated mutations and the placement on the chromosome clinches it.

              With central apnea you stop breathing - no obstructions are involved. I don't even have to be asleep to experience it.). If I have other similar symptoms I'm not aware of them, but I'm now curious.
              Awake breath holds are a part of LO-CCHS and not much else unless you are at high altitude or have serious COPD. It resembles Chenye-Stokes breathing but not quite. Chenye-Stokes is usually seen as people are near death or are seriously short on oxygen. You should see your doctor and have your kappa/lambda free light chains checked. That is the most deadly side effect of piedaldism, the strong predilection to myeloma. Most doctors have never heard of piebaldism because it is so uncommon.

              Keep in mind that I am not a doctor so I am free to give medical advice. Also remember it's worth what you paid for it. See your doctor for the real thing.
              Last edited by Evan; 11-02-2012, 04:22 PM.
              Free software for calculating bolt circles and similar: Click Here

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              • #8
                Knowing, as you now do, will help tremendously, esp the mindset. Plus that last line is no small bit of importance. I can't imagine how it feels.
                I showed this to my doctor. He is extremely critical and requires close to absolute proof before he will accept my evidence on anything. When he saw this it took about 2 minutes and he was completely convinced. Every doctor know enough about genetics to understand how definitive this is. A matchup like this simply cannot be coincidence, especially when there are absolutely no differential diagnoses. That means there are no other plausible explanations that take into account all the presenting symptoms. This one does and perfectly too.

                And yes, knowing with certainty that our kids don't have it is a huge relief. We have two children and coin flipped in their favour each time.
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                • #9
                  Originally posted by Evan View Post

                  And yes, knowing with certainty that our kids don't have it is a huge relief. We have two children and coin flipped in their favour each time.
                  I dont know if there is a "best" part to this story, except maybe what hard work can bring, but the above is definatly the icing on cake...

                  Is there a luck gene? Maybe you passed that one on too...

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                  • #10
                    Evan,

                    Wow. Its tough to figure out what to say, but a whole lot easier than to deal with your condition. Now that the cause has been pinned down what can be done? Given you and your cousin have beaten the short longevity odds coupled with the rarity of the disease is there anyone who has researched it and found someway to at least control it?

                    I wish you well and hope you can at least find some relief.

                    Stan

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                    • #11
                      Wishing you also the best from here Evan.

                      (This place seems strange at times without your'e postings!!)

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                      • #12
                        So I guess you can stop blaming the chemicals you worked with back in your photocopy days?

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                        • #13
                          No chemicals or other environmental variables. The old nature vs nurture argument is finally settled. Nature (genetics) has the big stick and nurture just sometimes kicks off what genes may be expressed. EVERYTHING is genetic. Environment can change that by causing mutations and it can change what genes kick into gear to deal with environmental stressors. The system is incredibly complex. The piebald (KIT) gene is one of the big players. Every cell has every gene but depending on what the cell does for a living many of the genes are suppressed so most mutations have no effect in those cells. The KIT gene is different from most. It is responsible for acting as a receptor for a chemical signalling agent, Tyrosine Kinase. That is used by many other cells in the body and especially mast cells, aka stem cells. Mast cells are everywhere and are a major part of the immune system. KIT is also responsible for melanin which it what give our skin and hair colour. However, melanin has a lot more purposes than that. It also is used in the ear as part of the cochlea and if missing you don't have hearing. That also applies to many other mechanisms in the body. I still haven't researched all the possibilities and there are many.

                          Right off the top the KIT receptors directly control the activation of about 20 other genes, including one that controls angiogenesis. That is the production of new blood vessels including in the brain. My stroke has been diagnosed as a burst ateriovenous malformation (AVM) and the AVM was most likely produced by an out of control gene that should be modulated by KIT. If the KIT receptor in any cell isn't working right then the Tyrosine Kinase signals don't act as they should.

                          I think there is a good possibility that now that I know what is going wrong at the bottom level I may be able to figure out some treatments to reduce some of the effects. This sort of problem is so rare that there are no attempts being made to figure out how to control it. They are only just approaching figuring out how to recognize these types of problems. I have already found one very likely connection that nobody seems to be aware of. That isn't the least surprising since the flood of new possibilities is overwhelming for the research community.
                          Last edited by Evan; 11-02-2012, 07:43 PM.
                          Free software for calculating bolt circles and similar: Click Here

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                          • #14
                            Good to hear you have a definite answer,sometimes just knowing is a relief.

                            So one question,when do we get to see pictures of all the cool home built gene splicing and re-sequencing equipment that you are no doubt dreaming up?
                            I just need one more tool,just one!

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                            • #15
                              Welcome back Evan!
                              Location: Saskatoon, Saskatchewan, Canada

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