The impact of spermine synthase (SMS) mutations on brain morphology
- 132 Downloads
Snyder–Robinson syndrome (SRS) is a form of X-linked mental retardation resulting from mutations in spermine synthase (SMS), which impact neurodevelopment and cognitive outcome. We obtained cerebral, cerebellum, hippocampus, and red nucleus volumes from two males with SRS and 24 age- and gender-matched typically developing controls using volumetric neuroimaging analyses. Total brain volume was enlarged in males with SRS while cerebellum, hippocampus, and red nucleus volumes tended to be reduced compared to controls. Mutations of the X chromosome may modulate the risk for mental retardation through altered early neurodevelopment, disruption in receptor function, and ongoing neural organization and plasticity. Disruption of SMS function may negatively affect regional brain volumes that subserve cognitive and motor abilities. This research provides valuable insight into the effects of polyamine function on brain development.
KeywordsSMS Spermine synthase Snyder–Robinson syndrome MRI Red nucleus Cerebellum Hippocampus Cerebrum
This research was supported by NIH grant HD 26202. The authors would like to acknowledge Dr. Booil Jo for her assistance with statistical methods.
- 2.Arena JF, Schwartz C, Ouzts L, Stevenson R, Miller M, Garza J, Nance M, Lubs H (1996) X-linked mental retardation with thin habitus, osteoporosis, and kyphoscoliosis: linkage to Xp21.3-p22.12. Am J Med Genet 64(1):50–58. doi: 10.1002/(SICI)1096-8628(19960712)64:1<50::AID-AJMG7>3.0.CO;2-V CrossRefPubMedGoogle Scholar
- 3.Cason AL, Ikeguchi Y, Skinner C, Wood TC, Holden KR, Lubs HA, Martinez F, Simensen RJ, Stevenson RE, Pegg AE, Schwartz CE (2003) X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet 11(12):937–944. doi: 10.1038/sj.ejhg.5201072 CrossRefPubMedGoogle Scholar
- 4.de Alencastro G, McCloskey DE, Kliemann SE, Maranduba CM, Pegg AE, Wang X, Bertola DR, Schwartz CE, Passos-Bueno MR, Sertie AL (2008) New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder-Robinson X-linked recessive mental retardation syndrome. J Med Genet 45(8):539–543. doi: 10.1136/jmg.2007.056713 CrossRefPubMedGoogle Scholar
- 10.Spiegel M, Schiller J, Srinivasan R (2000) Schaum's Outline of Probability and Statistics. McGraw-Hill, New YorkGoogle Scholar
- 11.Tukey J (1977) Exploratory data analysis. Addison-Wesley, ReadingGoogle Scholar
- 12.Ge Y, Grossman RI, Babb JS, Rabin ML, Mannon LJ, Kolson DL (2002) Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis. AJNR Am J Neuroradio 23(8):1327–1333Google Scholar
- 16.Yatin SM, Yatin M, Varadarajan S, Ain KB, Butterfield DA (2001) Role of spermine in amyloid beta-peptide-associated free radical-induced neurotoxicity. J Neurosci Res 63(5):395–401. doi: 10.1002/1097-4547(20010301) 63:5<395::AID-JNR1034>3.0.CO;2-Q CrossRefPubMedGoogle Scholar
- 23.Harney SC, Rowan M, Anwyl R (2006) Long-term depression of NMDA receptor-mediated synaptic transmission is dependent on activation of metabotropic glutamate receptors and is altered to long-term potentiation by low intracellular calcium buffering. J Neurosci 26(4):1128–1132CrossRefPubMedGoogle Scholar