@entity2057 ( @entity2057 ) is a devastating @entity74 caused by homozygous loss of @entity11280 . Rarely, @entity11280 -deleted individuals are fully asymptomatic despite carrying identical @entity23247 copies as their @entity2057 -affected siblings suggesting protection by genetic modifiers other than @entity23247 . High @entity16624 ( @entity16624 ) expression has previously been found in lymphoblastoid cells but not in fibroblasts of asymptomatic compared to symptomatic siblings. To find out whether @entity16624 is also upregulated in MNs of asymptomatic individuals and thus a convincing @entity2057 protective modifier, we generated induced pluripotent stem cells (iPSCs) from fibroblasts of three asymptomatic and three @entity2057 -affected siblings from two families and compared these to iPSCs from a @entity2057 @entity1 and control individuals. MNs were differentiated from iPSC-derived small molecule neural precursor cells (smNPCs). All four genotype classes showed similar capacity to differentiate into MNs at day 8. However, @entity2057 -derived MN survival was significantly decreased while @entity2057 - and asymptomatic-derived MN survival was moderately reduced compared to controls at day 27. SMN expression levels and concomitant gem numbers broadly matched @entity23247 copy number distribution; @entity2057 presented the lowest levels, whereas @entity2057 and asymptomatic showed similar levels. In contrast, @entity16624 was significantly upregulated in mixed MN cultures from asymptomatic individuals pinpointing a tissue-specific regulation. Evidence for strong @entity16624 accumulation in shaft and rim of growth cones in MN cultures from asymptomatic individuals implies an important role in neuromuscular synapse formation and maintenance. These findings provide strong evidence that @entity16624 is a genuine @entity2057 protective modifier.

@entity16624 is upregulated in iPSC-derived motoneurons from asymptomatic XXXX -deleted individuals.

@entity1 :: ('9606', 'Species') :: ['patient'] @entity23247 :: ('6607', 'Gene') :: ['SMN2'] @entity16624 :: ('5358', 'Gene') :: ['plastin 3', 'PLS3'] @entity74 :: ('MESH:D030342', 'Disease') :: ['motoneuron (MN) disorder'] @entity11280 :: ('6606', 'Gene') :: ['SMN1'] @entity2057 :: ('MESH:D009133', 'Disease') :: ['SMA I', 'Spinal muscular atrophy', 'SMA III', 'SMA']
@entity11280 :: (6606,Gene) :: ['SMN1']
