c.835-5T>G Variant in SMN1 Gene Causes Transcript Exclusion of Exon 7 and Spinal Muscular Atrophy.
Shuang WuYun-Lu LiNing-Yi ChengChong WangEn-Lin DongYing-Qian LuJin-Jing LiXin-Xin GuoXiang LinLu-Lu LaiZhi-Wei LiuNing WangWan-Jin ChenPublished in: Journal of molecular neuroscience : MN (2018)
Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder caused by survival motor neuron (SMN) protein deficiency leading the loss of motor neurons in the anterior horns of the spinal cord and brainstem. More than 95% of SMA patients are attributed to the homozygous deletion of survival motor neuron 1 (SMN1) gene, and approximately 5% are caused by compound heterozygous with a SMN1 deletion and a subtle mutation. Here, we identified a rare variant c.835-5T>G in intron 6 of SMN1 in a patient affected with type I SMA. We analyzed the functional consequences of this mutation on mRNA splicing in vitro. After transfecting pCI-SMN1, pCI-SMN2, and pCI-SMN1 c.835-5T>G minigenes into HEK293, Neuro-2a, and SHSY5Y cells, reverse transcription polymerase chain reaction (RT-PCR) was performed to compare the splicing effects of these minigenes. Finally, we found that this mutation resulted in the skipping of exon 7 in SMN1, which confirmed the genetic diagnosis of SMA.
Keyphrases
- spinal cord
- coronary artery disease
- percutaneous coronary intervention
- genome wide
- acute myocardial infarction
- copy number
- acute coronary syndrome
- end stage renal disease
- newly diagnosed
- antiplatelet therapy
- chronic kidney disease
- st elevation myocardial infarction
- induced apoptosis
- st segment elevation myocardial infarction
- gene expression
- spinal cord injury
- signaling pathway
- small molecule
- prognostic factors
- intellectual disability
- dna methylation
- cell proliferation
- case report
- heart failure
- patient reported outcomes
- cell death
- cell cycle arrest
- rna seq
- pi k akt