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The impact of spermine synthase (SMS) mutations on brain morphology

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Abstract

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.

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Acknowledgements

This research was supported by NIH grant HD 26202. The authors would like to acknowledge Dr. Booil Jo for her assistance with statistical methods.

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Authors and Affiliations

  1. Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, 401 Quarry Road, MC5795, Stanford, CA, 94305-5795, USA

    Shelli R. Kesler & Allan L. Reiss

  2. Greenwood Genetic Center, Greenwood, SC, USA

    Charles Schwartz & Roger E. Stevenson

Authors
  1. Shelli R. Kesler
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  2. Charles Schwartz
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  3. Roger E. Stevenson
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  4. Allan L. Reiss
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Corresponding author

Correspondence to Shelli R. Kesler.

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Supplementary Figure 1

Whole Brain Volumes Measurement: a Gray scale brain image (left) is separated into gray matter, white matter and CSF tissues, left to right, respectively, using a constrained fuzzy segmentation algorithm. Voxel shade represents the proportion of the specific tissue at that location (darker = increased). b Gray matter images are shown in multiplanar views in BrainImage. The Talairach stereotaxic grid (shown by dotted and solid lines) is used for positional normalization and parcellation of brain tissue into subregions. The Talairach sectors corresponding to the frontal lobe are outlined in solid lines. (PDF 1017 kb)

Supplementary Figure 2

Red Nucleus Volume Measurement. The anterior/posterior range of the red nucleus was defined in reference to the posterior commissure: drawn on the fourth through the sixth axial slices from posterior commissure. The superior boundary was the white matter bordering the thalamus (occasionally absent, in which case the rater used the thalamus itself). The substantia nigra formed the inferior boundary. The medial boundary consisted of a vertical line between the interpeduncular cistern and third ventricle, separating the two cerebral hemispheres. The lateral boundary was formed by the cerebral peduncle white matter tract, avoiding the darker gray matter of the subthalamic nuclei in posterior slices. (PDF 1017 kb)

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Kesler, S.R., Schwartz, C., Stevenson, R.E. et al. The impact of spermine synthase (SMS) mutations on brain morphology. Neurogenetics 10, 299–305 (2009). https://doi.org/10.1007/s10048-009-0184-2

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  • DOI: https://doi.org/10.1007/s10048-009-0184-2

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