Dec. 14 – On the internet, a missing link can be overall negligible.
However, in the enormously more complex system that is the human body, a link deficiency can produce serious damage. Recent research has linked children’s epilepsy with learning deficits consequences to a malignant disease on the X chromosome, revealing an epigenetic defect.
The study identifies the functional link in the complex maze of the molecular defects associated with this disease. The research was carried out by a team of researchers from the “Adriano Buzzati Traverso” CNR Institute of Genetics and Biophysics (CNR-Igb) of Naples, was funded by the French “Jerome Lejeune,” and finally published in the American Journal of Human Genetics (http://www.cell.com/AJHG/home). “The instability associated with epilepsy from triplet ARX gene, transcriptional activator of DNA, is a rare but devastating form of malignant epilepsy, occurring in the first months of life for boys,” says Maria Giuseppina Miano, Research Manager at the CNR-Igb. “Alterations of ARX trigger alterations on the KDM5C target gene, whose epigenetic regulator plays a key role in determining which genes will be activated to ensure the embryonic brain’s proper development.” The researcher stresses the novelty of this investigation, consisting in the discovery that “gene mutations ARX seriously damage the activation of KDM5C and, consequently, the downstream epigenetic control. This confirms a direct relationship between genetic damage and disease severity. To understand the underlying disease dynamics, the irregular interactions between the two genes and the effect this has on the defect differentiation of neurons have been analyzed. This has allowed the identification of a global alteration that occurs during the maturation of GABAergic neurons (a class of inhibitory interneurons severely damaged in sick children), causing an imbalance of functional genes.” This dysfunction produces serious consequences on affected children, who, from an early age, have a general disorganization and chaotic electrical discharges with impairment to brain maturation. This, in turn, shows defects in learning ability in the following years. “Hence it is necessary to provide these children with timely AEDs that intervene before they complete cognitive development. Unfortunately, newborns with these deficits often do not respond to conventional antiepileptic therapy – says Maria Giuseppina Miano. This study lays the foundation for further research aimed at developing new treatment methods for refractory epilepsy, limiting the damage that seizures produce on neurological development.”
