Objective: To investigate the potential association of plastin 3 (PLS3) expression levels in the blood with disease severity in spinal muscular atrophy (SMA).
Design: Measurement of PLS3 messenger RNA levels in the blood of patients with types I, II, and III SMA.
Setting: Pediatric Neuromuscular Clinical Research Network SMA Natural History study.
Participants: A cohort of 88 patients of both sexes who had SMA.
Main outcome measures: Levels of PLS3 messenger RNA in relation to SMA type and SMN2 copy number.
Results: Prepubertal female and younger male (<11 years) patients had approximately 2-fold-higher levels of PLS3 expression than did postpubertal female and older male (≥11 years) patients, respectively (P ≤ .001). Expression of PLS3 in male patients did not correlate with SMA clinical type or SMN2 copy number in either age group (P > .10). In postpubertal female patients, PLS3 expression was greatest in patients with type III SMA, was intermediate in patients with type II SMA, and was lowest in patients with type I SMA. Expression of PLS3 correlated with SMA type, SMN2 copy number, and the gross motor function measure only in postpubertal female patients.
Conclusion: The PLS3 gene may be an age- and/or puberty-specific and sex-specific modifier of SMA.