Using third-generation sequencing, researchers from China identified new types of SMN gene transcript variants and published their findings in Molecular Genetics and Genomics.

“The novel transcripts identified in our study expanded knowledge of the diversity of transcript variants generated from the SMN genes and showed a much more comprehensive profile of the SMN splicing spectrum,” Mengyao Dai, MD, and the coauthors of the study wrote.

These findings can help better understand the reason for low SMN protein expression and the pathogenesis of spinal muscular atrophy (SMA).

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In humans, there are 2 genes that encode the SMN protein, SMN1, and SMN2. These 2 genes have different patterns of alternative splicing.

The current study identified 36 types of transcript variants from the SMN1 and SMN2 genes, of which 18 were novel transcripts that had never been reported before. The authors said that an equal number of transcript variants were generated from each gene.

The different splicing events that gave rise to the different variants included exon skipping, shortening, and addition and intron retention.

Read more about the pathophysiology of SMA

The transcripts produced from the SMN1 gene included full-length SMN1 and SMN1 missing exons 3, 5, or 7. Those produced from the SMN2 gene mainly included SMN2 missing exon 7, followed by full-length SMN2, SMN2 missing exons 3 to 5, and SMN2 missing exons 5 to 7. 

The third-generation sequencing approach also called the long-read sequencing technique, used here “could accurately distinguish sequences of SMN1 from those of SMN2,” the authors said.

The protein that the SMN gene encodes is essential for the survival of motor neurons. When it is deficient, the alpha motor neurons in the anterior horn of the spinal cord degenerate, leading to progressive muscle weakness and loss of movement.


Dai M, Xu Y, Sun Y, et al. Revealing diverse alternative splicing variants of the highly homologous SMN1 and SMN2 genes by targeted long-read sequencing. Mol Genet Genomics. Published online May 25, 2022. doi:10.1007/s00438-022-01874-6