Abstract
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.
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Funding
This work was supported by the grants 81371261, 81771230, and U1505222 from the National Natural Science Foundation of China, National Key Clinical Specialty Discipline Construction Program, and Key Clinical Specialty Discipline Construction Program of Fujian.
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This study was approved by The Affiliated First Hospital of Fujian Medical University Ethics Committee and the informed consent was obtained from the parents of the patient.
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Wu, S., Li, YL., Cheng, NY. et al. c.835-5T>G Variant in SMN1 Gene Causes Transcript Exclusion of Exon 7 and Spinal Muscular Atrophy. J Mol Neurosci 65, 196–202 (2018). https://doi.org/10.1007/s12031-018-1079-1
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DOI: https://doi.org/10.1007/s12031-018-1079-1