Fig. 1

Normal SMN protein expression and in patients with spinal muscular atrophy. Survival motor neuron gene 1 (SMN1) encodes full length SMN protein needed to ensure survival of motor neurons and normal muscle growth and function (left). The nearly identical SMN2 gene differs by only two nucleotides, a CT base change inside exon 7 that affects gene splicing and leads to exon 7 skipping in the majority of SMN2 mRNA (messenger ribonucleic acids) (right). SMN2 mRNA transcripts with exon 7 included provide a supplementary source of normal SMN protein; SMN2 mRNA lacking exon 7 encodes truncated, rapidly degraded SMN protein. In patients with SMA, there is a homozygous deletion or loss of function of the SMN1 gene, eliminating the body’s main source of SMN protein (center). The functional protein made by the SMN2 gene is identical to that produced by the SMN1 gene but is produced in insufficient quantity to support normal motor neuron functioning, muscle growth, and development. SMN1 codes for full length functional SMN1 protein which is the primary source of the SMN protein. SMN2 with exon 7 included is a full length, functional SMN protein (10–20%). SMN2 with Exon 7 excluded is an unstable rapidly degraded SMN protein (80–90%). Patients with SMN may have up to eight copies of the SMN2 gene, all of which can produce limited quantities of SMN protein. Patients with more SMN2 gene copies generally have less severe SMA [12,13,14,15]. Figure property of Scholar Rock, Inc