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

Authors

Matthew E R Butchbach, Center for Applied Clinical Genomics, Nemours Children's Health Delaware, Wilmington, DE 19803, USA; Center for Pediatric Research, Nemours Children's Health Delaware, Wilmington, DE 19803, USA; Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA; Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA 19107, USAFollow

Document Type

Article

Publication Date

7-23-2021

Comments

This article is the author's final published version in International Journal of Molecular Sciences, Volume 22, Issue 15, August 2021, Article number 7896

The published version is available at https://doi.org/10.3390/ijms22157896.

Copyright © 2021 by the author. Licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Abstract

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 SMN1-SMN2 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.

Recommended Citation

Butchbach, Matthew E R, "Genomic Variability in the Survival Motor Neuron Genes (SMN1 and SMN2): Implications for Spinal Muscular Atrophy Phenotype and Therapeutics Development" (2021). Department of Pediatrics Faculty Papers. Paper 104.
https://jdc.jefferson.edu/pedsfp/104

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

34360669

Language

English