To find out whether PLS3 is also upregulated in MNs of asymptomatic individuals and thus a convincing SMA protective modifier, we generated induced pluripotent stem cells (iPSCs) from fibroblasts of three asymptomatic and three SMA III-affected siblings from two families and compared these to iPSCs from a SMA I patient and control individuals.
In conclusion, a significant proportion of patients with early-onset SMA classified as SMA II on the basis of achieved motor function turned out to be SMA III at later follow-up.