Dr. Charlotte Sumner explains how SMA is related to changes in the SMN1 and SMN2 genes.
In the general population, individuals who have a normal SMN1 gene, do not require the SMN2 gene. So there are many of us in fact who have no SMN2 gene when we retain a normal SMN1 gene. But in the case of an individual who has SMA when both copies of the SMN1 gene are mutated, they rely completely on the presence of an SMN2 gene an in fact every patient with SMA retains at least one copy of the SMN2 gene.
That gene is very similar to SMN1 almost identical, but it has a few changes in its spelling, in its sequence and one of those changes in particular, in fact a single change results in a difference in the way the RNAs that result from that gene are processes. And as a result, those RNAs most of the time that come from this SMN2 gene are too short. They lack an exon we call exon7 and that protein that's made from those RNAs that lack exon 7 is also too short and very, very unstable and becomes degraded very quickly.
Some of the time, the RNA that comes from the SMN2 gene does retain exon 7. It's spliced so that it includes exon 7. It makes a normal length RNA molecule, a normal SMN protein and that little bit of SMN protein that comes from SMN2 is adequate to allow a child with SMA to be born. But unfortunately that reduced level of SMN protein makes motor neurons sick and motor neurons degenerate that's causing the disease SMA.
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