1. Hom CL, Touchette P, Nguyen V, Fernandez G, Tournay A, Plon L, Himber P, Lott IT. {{The relationship between living arrangement and adherence to antiepileptic medications among individuals with developmental disabilities}}. {J Intellect Disabil Res};2014 (Mar 11)
BACKGROUND: Non-adherence to antiepileptic drugs (AEDs) is associated with considerable morbidity and mortality in the general population but little is known about adherence in individuals with intellectual disability (ID). METHOD: Using the records of a closed pharmacy billing system over a 30 month period, we examined the medication non-adherence rates for AEDs among 793 individuals with ID. We calculated the medication possession ratio (number of days each participant was in possession of an AED), and defined non-adherence as 25% or more of the exposure days without the possession of an AED. All participants studied had filled prescriptions for AEDs spanning at least 6 months. RESULTS: Controlling for age and gender, we found non-adherence rates varied by living arrangement. Compared with those living in group homes, individuals with ID living in family homes or in semi-independent settings were significantly less adherent to AEDs (P < 0.0003). CONCLUSION: Non-adherence to AEDs is a potential medical risk for individuals with ID that is significantly impacted by the type of community living arrangement.
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2. Jaramillo TC, Liu S, Pettersen A, Birnbaum SG, Powell CM. {{Autism-Related Neuroligin-3 Mutation Alters Social Behavior and Spatial Learning}}. {Autism Res};2014 (Mar 11)
Multiple candidate genes have been identified for autism spectrum disorders. While some of these genes reach genome-wide significance, others, such as the R451C point mutation in the synaptic cell adhesion molecule neuroligin-3, appear to be rare. Interestingly, two brothers with the same R451C point mutation in neuroligin-3 present clinically on seemingly disparate sides of the autism spectrum. These clinical findings suggest genetic background may play a role in modifying the penetrance of a particular autism-associated mutation. Animal models may contribute additional support for such mutations as functionally relevant and can provide mechanistic insights. Previously, in collaboration with the Sudhof laboratory, we reported that mice with an R451C substitution in neuroligin-3 displayed social deficits and enhanced spatial learning. While some of these behavioral abnormalities have since been replicated independently in the Sudhof laboratory, observations from the Crawley laboratory failed to replicate these findings in a similar neuroligin-3 mutant mouse model and suggested that genetic background may contribute to variation in observations across laboratories. Therefore, we sought to replicate our findings in the neuroligin-3 R451C point mutant knock-in mouse model (NL3R451C) in a different genetic background. We backcrossed our NL3R451C mouse line onto a 129S2/SvPasCrl genetic background and repeated a subset of our previous behavioral testing. NL3R451C mice on a 129S2/SvPasCrl displayed social deficits, enhanced spatial learning, and increased locomotor activity. These data extend our previous findings that NL3R451C mice exhibit autism-relevant behavioral abnormalities and further suggest that different genetic backgrounds can modify this behavioral phenotype through epistatic genetic interactions. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Liyanage VR, Rastegar M. {{Rett Syndrome and MeCP2}}. {Neuromolecular Med};2014 (Mar 11)
Rett syndrome (RTT) is a severe and progressive neurological disorder, which mainly affects young females. Mutations of the methyl-CpG binding protein 2 (MECP2) gene are the most prevalent cause of classical RTT cases. MECP2 mutations or altered expression are also associated with a spectrum of neurodevelopmental disorders such as autism spectrum disorders with recent links to fetal alcohol spectrum disorders. Collectively, MeCP2 relation to these neurodevelopmental disorders highlights the importance of understanding the molecular mechanisms by which MeCP2 impacts brain development, mental conditions, and compromised brain function. Since MECP2 mutations were discovered to be the primary cause of RTT, a significant progress has been made in the MeCP2 research, with respect to the expression, function and regulation of MeCP2 in the brain and its contribution in RTT pathogenesis. To date, there have been intensive efforts in designing effective therapeutic strategies for RTT benefiting from mouse models and cells collected from RTT patients. Despite significant progress in MeCP2 research over the last few decades, there is still a knowledge gap between the in vitro and in vivo research findings and translating these findings into effective therapeutic interventions in human RTT patients. In this review, we will provide a synopsis of Rett syndrome as a severe neurological disorder and will discuss the role of MeCP2 in RTT pathophysiology.
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4. Lokody I. {{Epigenetics: Mechanisms underlying fragile X syndrome}}. {Nat Rev Genet};2014 (Mar 11)
