• Halsey’s article and SMN copies

    Posted by lupa-f on February 26, 2022 at 9:28 am

    So Halsey’s article today made me wonder if I was misunderstanding SMA and SMN1 and 2 with this passage: “but there’s another piece of information in my chart from my original diagnostic blood test in 1999 that further explains why they find my case to be particularly intriguing: I have zero copies of the survivor motor neuron 1 (SMN1) gene.

    This gene carries the instructions for building SMN protein, which creates muscle. The fewer copies of it that someone has, the more severe their SMA should be.

    Additionally, I have only two copies of the SMN2 gene, which supplements SMN1.”

    After doing some checking, I think this section is off. Almost all cases of SMA will show zero copies of SMN1, that’s how it’s confirmed. A carrier will have 1, and normal will have 2 (with some occasional rare differences). It’s the number of copies of SMN2 that usually determine severity, but we know that’s not a hard rule.

    https://clevelandcliniclabs.com/2017/10/18/tb-spinal-muscular-atrophy-copy-number-analysis/#sma-tb-interpretation: “Among patients with clinical presentations suggestive of SMA, detection of zero SMN1 copies confirms the diagnosis.”


    anna replied 2 years, 4 months ago 3 Members · 5 Replies
  • 5 Replies
  • deann-r

    February 26, 2022 at 9:58 am

    Lupa, I don’t think you’re misunderstanding SMA at all. I believe Halsey is relaying the information given to her as she processed it. It’s not meant for scientific fact. Genetics are very complex. Heck I just fumbled trying to explain it to my new nurse and I certainly should have it figured out by now. As far as I know, if you have a deletion (0 copies) of SMN1 you have SMA. Of course there are mutations and whatnot. If you have one copy you’re considered a carrier like you said. I believe there is a big correlation between SMN2 and severity but a lot of other things factor into that.

    • lupa-f

      March 1, 2022 at 2:42 pm

      Was there some reason my previous response to this was deleted? That’s some pretty shady moderation.

  • anna

    February 27, 2022 at 5:20 am

    I doubt the correlation between SMN2 and severity is that critical either. I have four copies of SMN2, which is a bit rare for type II, and yet I know of cases with three or even two copies that are less severe than mine.

    • lupa-f

      February 27, 2022 at 3:07 pm

      The correlation is definitely not 100%, for instance I have 3 copies and am a definite type 3 and many of the type 2s here also have 3. In that terrible IQ study that was posted here a bit ago, there was a type 1 that I think had 6 copies.

      But the amount of copies does make a clear difference in some respects: During the early Spinraza trials those with 3 copies did much better in general than those with 2 (I don’t think they had other amounts in that trial).

      • anna

        March 2, 2022 at 1:56 pm

        I had no idea about the Spinraza trials, I wonder if there were any similar observations with Evrysdi too…

        Btw, about that IQ study, would you mind elaborating a bit on the word “terrible”? Sorry for going off topic, I’m just curious because my sister, who is a doctor, also thinks it’s unreliable. Of course, there’s a chance she’s only trying to make me feel better about the fact that I might be getting dumber with time lol

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