Association of SHANK Family with Neuropsychiatric Disorders: An Update on Genetic and Animal Model Discoveries.

The Shank family proteins are enriched at the postsynaptic density (PSD) of excitatory glutamatergic synapses. They serve as synaptic scaffolding proteins and appear to play a critical role in the formation, maintenance and functioning of synapse. Increasing evidence from genetic association and animal model studies indicates a connection of SHANK genes defects with the development of neuropsychiatric disorders. In this review, we first update the current understanding of the SHANK family genes and their encoded protein products. We then denote the literature relating their alterations to the risk of neuropsychiatric diseases. We further review evidence from animal models that provided molecular insights into the biological as well as pathogenic roles of Shank proteins in synapses, and the potential relationship to the development of abnormal neurobehavioral phenotypes.

Blood DNA methylation pattern is altered in mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) is a common epileptic disorder; little is known whether it is associated with peripheral epigenetic changes. Here we compared blood whole genomic DNA methylation pattern in MTLE patients (n = 30) relative to controls (n = 30) with the Human Methylation 450 K BeadChip assay, and explored genes and pathways that were differentially methylated using bioinformatics profiling. The MTLE and control groups showed significantly different (P < 1.03e-07) DNA methylation at 216 sites, with 164 sites involved hyper- and 52 sites hypo- methylation. Two hyper- and 32 hypo-methylated sites were associated with promoters, while 87 hyper- and 43 hypo-methylated sites corresponded to coding regions. The differentially methylated genes were largely related to pathways predicted to participate in anion binding, oxidoreductant activity, growth regulation, skeletal development and drug metabolism, with the most distinct ones included SLC34A2, CLCN6, CLCA4, CYP3A43, CYP3A4 and CYP2C9. Among the MTLE patients, panels of genes also appeared to be differentially methylated relative to disease duration, resistance to anti-epileptics and MRI alterations of hippocampal sclerosis. The peripheral epigenetic changes observed in MTLE could be involved in certain disease-related modulations and warrant further translational investigations.