c.835-5T>G Variant in SMN1 Gene Causes Transcript Exclusion of Exon 7 and Spinal Muscular Atrophy

• Published in: Journal of molecular neuroscience Vol. 65; no. 2; pp. 196 - 202
• Main Authors: Wu, Shuang, Li, Yun-Lu, Cheng, Ning-Yi, Wang, Chong, Dong, En-Lin, Lu, Ying-Qian, Li, Jin-Jing, Guo, Xin-Xin, Lin, Xiang, Lai, Lu-Lu, Liu, Zhi-Wei, Wang, Ning, Chen, Wan-Jin
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2018; Springer Nature B.V
• Subjects: Atrophy; Autosomal recessive inheritance; Biomedical and Life Sciences; Biomedicine; Brain stem; Cell Biology; Clonal deletion; Gene deletion; Genetic disorders; Genetic screening; Hereditary diseases; Motor neurons; Mutation; Neurochemistry; Neurology; Neuromuscular diseases; Neurosciences; Polymerase chain reaction; Protein deficiency; Proteins; Proteomics; Reverse transcription; SMN protein; Spinal cord; Spinal muscular atrophy; Splicing; Survival; Splice variant; Exon skipping; Survival motor neuron 1; Spinal muscular atrophy
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1007/s12031-018-1079-1

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.