1. Forlani G, Giarda E, Ala U, Di Cunto F, Salani M, Tupler R, Kilstrup-Nielsen C, Landsberger N. {{The MeCP2/YY1 interaction regulates ANT1 expression at 4q35: novel hints for Rett syndrome pathogenesis}}. {Hum Mol Genet} (May 26)
Rett syndrome is a severe neurodevelopmental disorder mainly caused by mutations in the transcriptional regulator MeCP2. Although there is no effective therapy for Rett syndrome, the recently discovered disease reversibility in mice suggests that there are therapeutic possibilities. Identification of MeCP2 targets or modifiers of the phenotype can facilitate the design of curative strategies. To identify possible novel MeCP2 interactors we exploited a bioinformatic approach and selected YY1 (Ying Yang 1) as an interesting candidate. We demonstrate that MeCP2 interacts in vitro and in vivo with YY1, a ubiquitous zinc-finger epigenetic factor regulating the expression of several genes. We show that MeCP2 cooperates with YY1 in repressing the ANT1 gene encoding a mitochondrial adenine nucleotide translocase. Importantly, ANT1 mRNA levels are increased in human and mouse cell lines devoid of MeCP2, in Rett patient fibroblasts, and in the brain of Mecp2-null mice. We further demonstrate that ANT1 protein levels are upregulated in Mecp2-null mice. Finally, the identified MeCP2-YY1 interaction, together with the well-known involvement of YY1 in the regulation of D4Z4 associated genes at 4q35, led us to discover the anomalous depression of FRG2, a subtelomeric gene of unknown function, in Rett fibroblasts. Collectively, our data indicate that mutations in MeCP2 might cause the aberrant overexpression of genes located at a specific locus thus providing new candidates for the pathogenesis of Rett syndrome. Since both ANT1 mutations and overexpression have been associated with human diseases, we consider of high relevance to address the consequences of ANT1 deregulation in Rett syndrome.
2. Lemon JM, Gargaro B, Enticott PG, Rinehart NJ. {{Brief Report: Executive Functioning in Autism Spectrum Disorders: A Gender Comparison of Response Inhibition}}. {J Autism Dev Disord} (May 27)
Although autism spectrum disorders (ASD) affect more males than females, it is not clear whether neurobehavioural correlates of ASD are equivalent across genders. This study examined gender differences in neurobehavioural functioning in boys and girls with ASD. Participants were males with ASD (n = 10), females with ASD (n = 13), typically developing males (n = 8), and typically developing females (n = 14). Each completed the stop task, a common measure of response inhibition. Females with ASD demonstrated a significant increase in stopping time (indicating poorer inhibition). By contrast, no response inhibition impairments were evident among males with ASD. Females with ASD may have a different neurobehavioural profile, and therefore different clinical needs, when compared with males with ASD.
3. Liu KY, King M, Bearman PS. {{Social influence and the autism epidemic}}. {Ajs} (Mar);115(5):1387-1434.
Despite a plethora of studies, we do not know why autism incidence has increased rapidly over the past two decades. Using California data, this study shows that children living very close to a child previously diagnosed with autism are more likely to be diagnosed with autism. An underlying social influence mechanism involving information diffusion drives this result, contributing to 16% of the increase in prevalence over 2000-2005. We eliminate competing explanations (i.e., residential sorting, environmental toxicants, and viral transmission) through seven tests and show that information diffusion simultaneously contributed to the increased prevalence, spatial clustering, and decreasing age of diagnosis.
