Spinal muscular atrophy: position and functional importance of the branch site preceding SMN exon 7.

In spinal muscular atrophy, the SMN1 gene is deleted or destroyed by mutation, while the neigboring, nearly identical SMN2 gene acts as a partial functional substitute. However, due to a single nucleotide exchange, the seventh exon of SMN2 is mostly excluded from the mature mRNA, and the resulting shorter protein is non-functional. Here, we map the previously uncharacterized intron 6 branch point by RT-PCR. Moreover we show that exon 7 inclusion can be either abolished or improved by mutations in this branch site region.