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Review

Genomic Variability in the Survival Motor Neuron Genes (SMN1 and SMN2): Implications for Spinal Muscular Atrophy Phenotype and Therapeutics Development

1
Center for Applied Clinical Genomics, Nemours Children’s Health Delaware, Wilmington, DE 19803, USA
2
Center for Pediatric Research, Nemours Children’s Health Delaware, Wilmington, DE 19803, USA
3
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
4
Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA 19107, USA
Academic Editor: James N. Sleigh
Int. J. Mol. Sci. 2021, 22(15), 7896; https://doi.org/10.3390/ijms22157896
Received: 28 June 2021 / Revised: 14 July 2021 / Accepted: 21 July 2021 / Published: 23 July 2021
(This article belongs to the Special Issue Genetics of Spinal Muscular Atrophy)
Spinal muscular atrophy (SMA) is a leading genetic cause of infant death worldwide that is characterized by loss of spinal motor neurons leading to muscle weakness and atrophy. SMA results from the loss of survival motor neuron 1 (SMN1) gene but retention of its paralog SMN2. The copy numbers of SMN1 and SMN2 are variable within the human population with SMN2 copy number inversely correlating with SMA severity. Current therapeutic options for SMA focus on increasing SMN2 expression and alternative splicing so as to increase the amount of SMN protein. Recent work has demonstrated that not all SMN2, or SMN1, genes are equivalent and there is a high degree of genomic heterogeneity with respect to the SMN genes. Because SMA is now an actionable disease with SMN2 being the primary target, it is imperative to have a comprehensive understanding of this genomic heterogeneity with respect to hybrid SMN1SMN2 genes generated by gene conversion events as well as partial deletions of the SMN genes. This review will describe this genetic heterogeneity in SMA and its impact on disease phenotype as well as therapeutic efficacy. View Full-Text
Keywords: spinal muscular atrophy; copy number variation; SMN1; SMN2; modifier gene; precision medicine; therapeutics; gene conversion; hybrid gene spinal muscular atrophy; copy number variation; SMN1; SMN2; modifier gene; precision medicine; therapeutics; gene conversion; hybrid gene
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MDPI and ACS Style

Butchbach, M.E.R. Genomic Variability in the Survival Motor Neuron Genes (SMN1 and SMN2): Implications for Spinal Muscular Atrophy Phenotype and Therapeutics Development. Int. J. Mol. Sci. 2021, 22, 7896. https://doi.org/10.3390/ijms22157896

AMA Style

Butchbach MER. Genomic Variability in the Survival Motor Neuron Genes (SMN1 and SMN2): Implications for Spinal Muscular Atrophy Phenotype and Therapeutics Development. International Journal of Molecular Sciences. 2021; 22(15):7896. https://doi.org/10.3390/ijms22157896

Chicago/Turabian Style

Butchbach, Matthew E. R. 2021. "Genomic Variability in the Survival Motor Neuron Genes (SMN1 and SMN2): Implications for Spinal Muscular Atrophy Phenotype and Therapeutics Development" International Journal of Molecular Sciences 22, no. 15: 7896. https://doi.org/10.3390/ijms22157896

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