Comment by at-fates-hands | Hacker News Reader

Comment by at-fates-hands | Hacker News Reader

Having lost a grandfather and an aunt to ALS, I can completely relate to what this family is going through. It is heartbreaking, and emotionally draining to watch someone go through it.

It also scares the crap out me knowing this is a genetic disease and two of my family members have already succumbed to it. This is known as Familial ALS. Genetically speaking, it comes down to a 50/50 chance I could get it. I can get screened to know for sure if I'll get it, but it requires you do counseling before you even take the tests, considering how it could change your life overnight.

Here's some facts about Familial ALS:

http://www.alsa.org/als-care/familial-als/familial-als.html

- Familial ALS- occurring more than once in a family and accounts for 5 to 10% of all cases.

- In 1991 a team of ALS Association-funded researchers linked familial ALS to chromosome 21. In 1993 the research team identified the precise defect, a change in the DNA for the protein called copper-zinc superoxide dismutase 1 (SOD1). Researchers since have found more than 100 mutations in different places in the coded DNA instructions for making SOD1.

It's frustrating because it seems like every time they get close to finding THE mutated gene, they identify several hundred others. It's like a game where the goal posts in a game are constantly changing.

I'm a SOD1 researcher and my heart goes out to you and the many patients suffering with this terrible disease and their families. Though rest assured, we're working hard to uncover why this happens and what we can do about it.

I just wanted to clarify some points. I'm not sure what you mean about "the mutated gene". SOD1 mutations definitely cause ALS. It's just that there isn't a single SOD1 mutation that's responsible. Over 100 different mutations of the same gene can lead to the disease. Other genes are also implicated in ALS, such as TDP-43 and FUS. Sure there are other genetic factors responsible for ALS, many of which are yet unknown. But these are known factors.

I would be very hesitant to sequence my SOD1 gene to be honest. Let's say it came up with a new mutation. Not all mutations will lead to disease. So while this may not cause you to get ALS in the long run, it may lead to you worrying incessantly as you get older. Furthermore, most of these 100+ mutations have only been found in a single family or even a single patient. It's quite possible there are other genetic polymorphisms in these families that make these patients susceptible to their SOD1 mutations. Also there are examples of SOD1 mutations that aren't 100% penetrant. That is if you have the mutation, you aren't 100% guaranteed to get the disease. For instance, in scandinavian populations the aspartate 90 to valine mutation is recessive.

Basically there are a lot of complicating factors. Even if your SOD1 gene comes back as the normal sequence, you couldn't know you were safe. That is unless you knew that your grandfather and aunt actually had SOD1 mutations. Of course these are only my opinions as a scientist. I am not a physician.

So... do the counseling! Knowing that the answer is out there for the taking is already changing your life, probably for the worst. "What is true is already so. Owning up to it doesn't make it worse..."

Have you not heard of "ignorance is bliss"? I don't see the point of knowing the answer here.

Because one day you will stumble or your grip will be weak and you'll spend all your time wondering if it was just the beginning signs of developing ALS or if you were just tired or clumsy. I would think that would be the point, at least for me.

- EDIT: for clarity.

I agree it would be nice if the option was still available to the OP. However he already knows what ALS is, that the gene is in his family and that he personally is "likely" to have it. More over, the two relatives lost to ALS are not mere statistics, but carry deep emotional implications that color every rational attempt at dealing with it.

Assuming the 50-50 estimate is accurate, the OP has a 50% chance of being released of this dreadful fear by being shown not to have the gene himself, which its a huge gain. On the other hand, I doubt it'd be much worse to know for sure to be a carrier of the disease. In the best case, there is much emotional work that can be done in putting their affairs in order and being a much need grief process.

I understand your point of view but I guess this topic is highly subjective. In my case, not knowing wouldn't bother me that much and knowing I don't have the gene wouldn't dramatically improve my life. However, knowing I have the gene would probably make me dramatically depressed for my remaining years.

Counseling is still available, it's just something I try not to think about it too much. It's not something I want to be constantly thinking about. You're right, losing two family members to the disease does burden me at times when I stop to think about it.

Here is a link to the inheritance chart which describes most situations and the likely hood it will passed on, and to which side (male or female) passes it on.

http://ghr.nlm.nih.gov/handbook/inheritance/riskassessment

If suppressing the thoughts works for you, great. Every one has to go through it at their own pace. Best wishes to you and your loved ones.

Won't a gene test from, eg 23andMe, reveal the ALS risks due to present markers, without requiring counseling?

Known makers make up less than half of known hereditary cases of ALS. That is in families with a history of ALS, only about 30-40% cases have been tracked down to mutations in a single gene. SOD1 mutations are the most common form of familial ALS but like I said, if you had a novel mutation, meaning one that hadn't been observed before, you'd really have no idea. Also if you have one of many previously identified mutations that have been observed in only a few or even a single patient, you still couldn't be sure you'd get ALS.

I couldn't imagine preparing yourself with counselling just to prepare to find out if you have ALS or any other life changing disease. That thought just blows me away.

I remember a couple of years ago coming out a clinic where I was told I have a kidney disease and if not treated within the next half decade I could die of kidney failure in the next 15 to 20 years and remember feeling pist off and indignant about it like: "Dammit! Why me? I'm a good person. I didn't do anything majorly wrong in life!" and now that I'm 4 1/2 months into my treatment I am being humbled by amazing people who have been dealt a much, much, much worse hand in life who have a better outlook on life.

I sure hope you don't get it. And whether or not you believe in God, I say to you, God be with you, and may he watch over you and your family.

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