5 ms·

My son too has a unique and disabling mutation. As far as I know, he is the only person with this mutation, but there are more people with a mutation in the sam

My son too has a unique and disabling mutation. As far as I know, he is the only person with this mutation, but there are more people with a mutation in the same region of the gene, that are affected in the same way. The problem with some mutations like this, is that they have an effect on the development of the brain from the start of the development and that fixing the gene (or better its RNA transscription) will not undo that development. The results of IQ tests seems to indicate that with my sons mutation, there is a problem with the myelination in his brain. Myeliniation is a process that starts before birth and continues into adolescent. At the moment he is quite happy and functioning well within his limits. His 'academic' IQ is rather low, but in some areas, he surpases the average person by far. He has a great sense of humor and people like him. In his case, I am really afraid what would happen if we would administer him a drug that would compensate for the genetic defect. Would he go through another fase of brain development and having to cope with all kinds of changes. Could he end up being less happy, because it would remove his ignorance about certain things. For example, at the moment he has no desire for a romantic relationship, but getting such a desire and than still not being able to satisfy it, could make him very unhappy.

tapland 7y ago
I have one as well that is herideraty but no relatives have it (tested after finding out I had it). I think it's usually something like 1 in 400k people having a mutation of a specific gene.
- fjfaase 7y ago
  De novo mutations (DNM), that is new mutations, is rather high and increases stronly with the age of the father, because sperm cells are produced by continued cell divisions, where the egg cells of women are produced before birth. With the mother there is also a slight increase over time, but the number of even old mothers is lower than that of young fathers. Luckily, only a small part of the DNM occur in genes and some mutations are not even harmfull, due to how triplets of base pairs are decoded into amino-acids. And then there are also many mutations that do have an effect on the protein being produced, but that the difference does not have a great effect. For most genes there are many variants, which all leads to working proteins, some of which might work slightly better than others in some area and maybe (slightly) better in another area. (Just recently there was a news item about how humans lack a certain gene compared to other mamals, which increases our risk with respect to cardiovascular disease, but apparently also increases our ability to walk/run long distances.)
  - sls 7y ago
    > the egg cells of women are produced before birth just fyi this is actually an active research topic, c.f. https://en.wikipedia.org/wiki/Oogonial_stem_cells#Research https://en.wikipedia.org/wiki/Oogonial_stem_cells#Research
air7 7y ago
That's a very powerful point. Every treatment (nay everything) is a one-way door: You do something, and there's no going back. With general medicine you can at least infer some knowledge based on other people's reaction to the same drug. But in "N-of-1" drugs, you're left completely in the dark. It's (going to be) a very hard call to make.
sslapec 7y ago
Flowers for Algernon by Daniel Keyes is exactly about this topic.
- jpittis 7y ago
  I interpreted it more as a story about aging. I guess both!
- mhb 7y ago
  As is Asimov's The Secret Sense: https://archive.org/details/TheSecretSense https://archive.org/details/TheSecretSense
- radicalbyte 7y ago
  Beat me to it. Fantastic book.
DoreenMichele 7y ago
If you know the specific issue -- the pathway the problem follows -- you may be able to do something about it more gently than some big irreversible drug. My firstborn son has a genetic disorder and a long list of issues. I figured I had until he was about five or so to do anything meaningful about it. This turned out to not be true. The window for intervention was much longer. He's 32 and much more functional than I ever expected him to be, though he still lives with me for now. He still has zero interest in a romantic relationship. He and I have the same genetic disorder. I do not share his general lack of interest in romantic relationships. I will suggest you try to not automatically lump in all of your child's characteristics with this one detail that he has a mutation. You might read up a bit on "ace" or "aromantic" people. There are people who just aren't terribly interested in romance. It's really not some bizarre defect.
- fjfaase 7y ago
  To clarify, the mutation of my son is not inherited, it is a new mutation, which most likely occured in my sperm cells. Not having an interest in romance is but one of the least symptoms he has. I only took it as an example. His social emotional development age is somewhere between 3 and 5 years. He can use a computer and loves watching children programs on YouTube. He has an above average autobiographical memory especially with respect to people who were with him. Most of the time, he knows who has been introduced to whom. He immediately notices when someone is missing who should be there. Very remarkable, because in general people are not good at this, especially not for groups over twenty people.
  - DoreenMichele 7y ago
    To clarify, the mutation of my son is not inherited, it is a new mutation, which most likely occured in my sperm cells. I did see your other comment. I did understand that this was new and apparently unique. https://news.ycombinator.com/item?id=20524334 https://news.ycombinator.com/item?id=20524334
radicalbyte 7y ago
Flowers for Algernon explores this issue and had a profound effect on me as a teenager. Probably the best book included in the school curriculum.
leemailll 7y ago
Is his motor function affected?
- fjfaase 7y ago
  Yes, his motor function is also affected, but has improved a lot, such that now as an adult, it is primarily his fine motor skills that are poor. But he has no problems using a mouse. The wear pattern of his shoes is still a little abnormal. The poor motor function is probably related to poor myelination of the nerves in his body, as his proprioception and pain perception are affected.
  - leemailll 7y ago
    Yeah, myelination usually has more pronounced effects on peripheral nerves as they had long wrapped axons. I’m glad your son did not have severe demyelination problem. I don’t want to sound brutal but the mild effect mutation caused could also be the reason he survived the mutation
    - fjfaase 7y ago
      He probably would not have survived when born a hunderd years ago or in a less developed country, because he relied on tube feeding for several years. To me, you did not sound brutal. A side effect of having better medical intervention techniques, is that the general fitness of human genetic material is getting lower. If you combine this with the higher age at which children are conceived, it might make genetic genering inevitable in the future for the human species to survive.
      - leemailll 7y ago
        Yeah, I totally agree your point. The better medical condition inevitably making those mutations deadly years ago now survivable. These conditions are also called rare diseases by NIH. They won’t worth the effort for pharma to develop traditional treatment. But genetic manipulation like crispr might help to cure, it might be late for your son, but might still helps.
xkcd-sucks 7y ago
Romantic relationships make lots of totally normal people very unhappy, to the point where perfectly healthy young people kill themselves over romantic rejection or kill partners for whatever reason. Learning how to do romantic relations is painful, and when it's not painful for a person, they usually experience the pain later when they get old or fall in with a terrible partner. So, your example of the happiness / awareness tradeoff really applies to everyone. It probably applies to ancient myths like Adam+Eve, Prometheus etc. too. From history it is clear that seeking awareness at the risk of existential discomfort is something that people do.
samirm 7y ago
Happiness is only understood in contrast. On the one hand you obviously want to protect your child and ensure their happiness, but on the other, by doing so, you might be robbing them of the essential human experience. Happiness shouldn't be an end goal to a life, but a byproduct of one. Negative experiences shouldn't be looked down upon and avoided, after all that is how we learn and improve ourselves - by overcoming adversity. Having said all that, this is an incredibly tough decision to make and is solely up to your family.
rohanseth 7y ago
I'm really sorry to hear about your son. I'm Lydia's father (the author of the medium post). What you shared is my biggest concern about going forward with Lydia's treatment. We are confident that the treatment will help her brain development, but to your point, there's a chance that will hurt her quality of life. We just don't know. How do you make a decision like that? I think about this a lot and don't have good answers. All I can say is that I have 3 goals for my daughter - and she doesn't need to be a 100% normal child to achieve any of those goals. 1) I hope my child is not in pain 2) I hope my child feels loved 3) I hope my child can find beauty in the world.
- max2 7y ago
  If I may make a suggestion (not sure if English is your second language or not). Consider using 'typical' instead of 'normal'. It took me awhile to get used to that but my daughter is better off this way.

tapland 7y ago

I have one as well that is herideraty but no relatives have it (tested after finding out I had it). I think it's usually something like 1 in 400k people having a mutation of a specific gene.

fjfaase 7y ago
De novo mutations (DNM), that is new mutations, is rather high and increases stronly with the age of the father, because sperm cells are produced by continued cell divisions, where the egg cells of women are produced before birth. With the mother there is also a slight increase over time, but the number of even old mothers is lower than that of young fathers. Luckily, only a small part of the DNM occur in genes and some mutations are not even harmfull, due to how triplets of base pairs are decoded into amino-acids. And then there are also many mutations that do have an effect on the protein being produced, but that the difference does not have a great effect. For most genes there are many variants, which all leads to working proteins, some of which might work slightly better than others in some area and maybe (slightly) better in another area. (Just recently there was a news item about how humans lack a certain gene compared to other mamals, which increases our risk with respect to cardiovascular disease, but apparently also increases our ability to walk/run long distances.)
- sls 7y ago
  > the egg cells of women are produced before birth just fyi this is actually an active research topic, c.f. https://en.wikipedia.org/wiki/Oogonial_stem_cells#Research https://en.wikipedia.org/wiki/Oogonial_stem_cells#Research

air7 7y ago

That's a very powerful point. Every treatment (nay everything) is a one-way door: You do something, and there's no going back. With general medicine you can at least infer some knowledge based on other people's reaction to the same drug. But in "N-of-1" drugs, you're left completely in the dark. It's (going to be) a very hard call to make.

sslapec 7y ago

Flowers for Algernon by Daniel Keyes is exactly about this topic.

jpittis 7y ago
I interpreted it more as a story about aging. I guess both!
mhb 7y ago
As is Asimov's The Secret Sense: https://archive.org/details/TheSecretSense https://archive.org/details/TheSecretSense
radicalbyte 7y ago
Beat me to it. Fantastic book.

DoreenMichele 7y ago

If you know the specific issue -- the pathway the problem follows -- you may be able to do something about it more gently than some big irreversible drug. My firstborn son has a genetic disorder and a long list of issues. I figured I had until he was about five or so to do anything meaningful about it. This turned out to not be true. The window for intervention was much longer. He's 32 and much more functional than I ever expected him to be, though he still lives with me for now. He still has zero interest in a romantic relationship. He and I have the same genetic disorder. I do not share his general lack of interest in romantic relationships. I will suggest you try to not automatically lump in all of your child's characteristics with this one detail that he has a mutation. You might read up a bit on "ace" or "aromantic" people. There are people who just aren't terribly interested in romance. It's really not some bizarre defect.

fjfaase 7y ago
To clarify, the mutation of my son is not inherited, it is a new mutation, which most likely occured in my sperm cells. Not having an interest in romance is but one of the least symptoms he has. I only took it as an example. His social emotional development age is somewhere between 3 and 5 years. He can use a computer and loves watching children programs on YouTube. He has an above average autobiographical memory especially with respect to people who were with him. Most of the time, he knows who has been introduced to whom. He immediately notices when someone is missing who should be there. Very remarkable, because in general people are not good at this, especially not for groups over twenty people.
- DoreenMichele 7y ago
  To clarify, the mutation of my son is not inherited, it is a new mutation, which most likely occured in my sperm cells. I did see your other comment. I did understand that this was new and apparently unique. https://news.ycombinator.com/item?id=20524334 https://news.ycombinator.com/item?id=20524334

radicalbyte 7y ago

Flowers for Algernon explores this issue and had a profound effect on me as a teenager. Probably the best book included in the school curriculum.

leemailll 7y ago

Is his motor function affected?

fjfaase 7y ago
Yes, his motor function is also affected, but has improved a lot, such that now as an adult, it is primarily his fine motor skills that are poor. But he has no problems using a mouse. The wear pattern of his shoes is still a little abnormal. The poor motor function is probably related to poor myelination of the nerves in his body, as his proprioception and pain perception are affected.
- leemailll 7y ago
  Yeah, myelination usually has more pronounced effects on peripheral nerves as they had long wrapped axons. I’m glad your son did not have severe demyelination problem. I don’t want to sound brutal but the mild effect mutation caused could also be the reason he survived the mutation
  - fjfaase 7y ago
    He probably would not have survived when born a hunderd years ago or in a less developed country, because he relied on tube feeding for several years. To me, you did not sound brutal. A side effect of having better medical intervention techniques, is that the general fitness of human genetic material is getting lower. If you combine this with the higher age at which children are conceived, it might make genetic genering inevitable in the future for the human species to survive.
    - leemailll 7y ago
      Yeah, I totally agree your point. The better medical condition inevitably making those mutations deadly years ago now survivable. These conditions are also called rare diseases by NIH. They won’t worth the effort for pharma to develop traditional treatment. But genetic manipulation like crispr might help to cure, it might be late for your son, but might still helps.

xkcd-sucks 7y ago

Romantic relationships make lots of totally normal people very unhappy, to the point where perfectly healthy young people kill themselves over romantic rejection or kill partners for whatever reason. Learning how to do romantic relations is painful, and when it's not painful for a person, they usually experience the pain later when they get old or fall in with a terrible partner. So, your example of the happiness / awareness tradeoff really applies to everyone. It probably applies to ancient myths like Adam+Eve, Prometheus etc. too. From history it is clear that seeking awareness at the risk of existential discomfort is something that people do.

samirm 7y ago

Happiness is only understood in contrast. On the one hand you obviously want to protect your child and ensure their happiness, but on the other, by doing so, you might be robbing them of the essential human experience. Happiness shouldn't be an end goal to a life, but a byproduct of one. Negative experiences shouldn't be looked down upon and avoided, after all that is how we learn and improve ourselves - by overcoming adversity. Having said all that, this is an incredibly tough decision to make and is solely up to your family.

rohanseth 7y ago

I'm really sorry to hear about your son. I'm Lydia's father (the author of the medium post). What you shared is my biggest concern about going forward with Lydia's treatment. We are confident that the treatment will help her brain development, but to your point, there's a chance that will hurt her quality of life. We just don't know. How do you make a decision like that? I think about this a lot and don't have good answers. All I can say is that I have 3 goals for my daughter - and she doesn't need to be a 100% normal child to achieve any of those goals. 1) I hope my child is not in pain 2) I hope my child feels loved 3) I hope my child can find beauty in the world.

max2 7y ago
If I may make a suggestion (not sure if English is your second language or not). Consider using 'typical' instead of 'normal'. It took me awhile to get used to that but my daughter is better off this way.