Editors' ChoiceEpigenetics

Turner Syndrome Reveals That X Marks the Spot for Imprinting

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Science Translational Medicine  22 May 2013:
Vol. 5, Issue 186, pp. 186ec84
DOI: 10.1126/scitranslmed.3006552

“She must get that from you.” Parents are often credited (or otherwise) with contributing to the traits of their offspring. Yet in some cases, an allele from a single parent actually can be preferentially expressed through genomic imprinting. Genomic imprinting is a heritable epigenetic process that results in the preferential expression of either the maternal or paternal allele for some genes. The function of this mysterious form of gene regulation is unknown. In 1997, David Skuse and colleagues discovered evidence for imprinting on the X chromosome in studies of female Turner syndrome patients, who are monosomic for the X chromosome. Skuse and colleagues reported that XpO individuals have better verbal and higher-order executive functions mediating social interactions as compared with those of XmO individuals. A cluster of X-linked imprinted genes was later discovered in mice in 2005. Despite these exciting insights, the influence of X-linked imprinting effects on human brain development and function have been greatly debated.

In a new study by Lepage et al., the authors demonstrate that significant differences exist in the brain morphology of Turner syndrome patients with XpO and XmO genotypes. Females with the XpO genotype have a thicker cortex in temporal regions, whereas females with the XmO genotype exhibit enlarged gray matter volume in the superior frontal regions. The brain region–specific effects on morphology suggest that imprinting on the X chromosome may act in a brain region–specific manner in humans. The authors control for many issues that may have confounded previous studies; in particular, they include a large number of Turner syndrome patients (23 XmO and 17 XpO) and control for age and hormone treatments. These new insights provide important information to understand the cognitive impairments associated with Turner syndrome. Further, the findings indicate the existence of sexually dimorphic imprinting effects and raise new questions about the identity and function of imprinted genes in the human brain.

J. F. Lepage et al., Genomic imprinting effects of the X chromosome on brain morphology. J. Neurosci. 33, 8567–8574 (2013). [Abstract]

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