Prior, T. W., Krainer, A. R., Hua, Y., Swoboda, K. J., Snyder, P. C., Bridgeman, S. J., Burghes, A. H. M., Kissel, J. T. (September 2009) A Positive Modifier of Spinal Muscular Atrophy in the SMN2 Gene. The American Journal of Human Genetics, 85 (3). pp. 408-413.
Abstract
Spinal muscular atrophy (SMA) is a common autosomal-recessive motor neuron disease caused by the homozygous loss of the SMN1 gene. A nearly identical gene, SMN2, has been shown to decrease the severity of SMA in a dose-dependent manner. However SMN2 is not the sole phenotypic modifier, because there are discrepant SMA cases in which the SMN2 copy number does not explain the clinical phenotype. This report describes three unrelated SMA patients who possessed SMN2 copy numbers that did not correlate with the observed mild clinical phenotypes. A single base substitution in SMN2, c.859G>C,, was identified in exon 7 in the patients' DNA. We now show that the change creates a new exonic splicing enhancer element and increases the amount of full-length transcripts, thus resulting in the less severe phenotypes. This demonstrates that the c.859G>C substitution is a positive modifier of the SMA phenotype and that not all SMN2 genes are equivalent. We have shown not only that the SMA phenotype is modified by the number of SMN2 genes but that SMN2 sequence variations can also affect the disease severity.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > exons > exon splicing bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > exons diseases & disorders > congenital hereditary genetic diseases > spinal muscular atrophy |
| CSHL Authors: | |
| Communities: | CSHL labs > Krainer lab CSHL Cancer Center Shared Resources > DNA Sequencing Service |
| Depositing User: | Matt Covey |
| Date: | 11 September 2009 |
| Date Deposited: | 20 Feb 2013 16:54 |
| Last Modified: | 30 Dec 2014 16:35 |
| PMCID: | PMC2771537 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27434 |
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