SMN1

About SMN1

SMN1 Survival Motor Neuron 1 on chromosome 5q13.2 encodes the SMN protein, which is essential for the assembly of small nuclear ribonucleoproteins used in messenger RNA splicing and is particularly critical for the survival of lower motor neurons in the spinal cord. Homozygous deletion or mutation of SMN1 causes spinal muscular atrophy, an autosomal recessive disease that was long one of the leading genetic causes of death in infancy. The gene was identified in 1995. SMA is classified into types by age of onset and highest motor milestone achieved. Type 1, also called Werdnig Hoffmann disease, begins in the first months of life with severe weakness and hypotonia, and without treatment children never sit independently and usually die in early childhood from respiratory failure. Types 2, 3, and 4 have progressively later onset and milder courses. A nearly identical neighboring gene, SMN2, mostly produces a truncated protein because of exon 7 skipping, but a small fraction of its transcripts are full length, so people with more SMN2 copies tend to have milder disease. Three disease modifying therapies are approved: nusinersen, an antisense oligonucleotide that promotes SMN2 exon 7 inclusion, risdiplam, an oral SMN2 splicing modifier, and onasemnogene abeparvovec, a gene therapy delivering SMN1 by AAV9 vector. Newborn screening allows treatment before symptoms begin.