1. Knight O, Bebbington A, Siafarikas A, Woodhead H, Girdler S, Leonard H. {{Pubertal trajectory in females with Rett syndrome: A population-based study}}. {Brain & development}. 2012 Dec 24.
Background: Rett syndrome is a severe genetic neurodevelopmental disorder mainly affecting females. The aim of this study was to describe pubertal development in a population-based cohort of females with Rett syndrome. Methods: To assess pubertal trajectory we used six waves of data provided by parents of girls and women, recruited through the Australian population-based Rett Syndrome Database. The age at which adrenarche, thelarche or menarche occurred was used as the parameter for time to event (survival) analysis. The relationships between BMI, mutation type and the trajectories were investigated, using Cox proportional hazards. Results: One quarter of girls reached adrenarche by 9.6years, half by 11years and three quarters by 12.6years. Half reached menarche by 14years (range 8-23). Being underweight was associated with later age at adrenarche, thelarche and menarche, while higher BMI (overweight) was associated with earlier onset. In general, girls with C-terminal deletions and early truncating mutations reached pubertal stages earlier and those with the p.R168X mutation reached them later. Conclusion: The pubertal course in Rett syndrome may be abnormal, sometimes with early adrenarche but delayed menarche. These features may be genotype dependent and may have varying relationships with growth and bone acquisition.
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2. Paul K, Venkitaramani D, Cox C. {{Dampened dopamine-mediated neuromodulation in prefrontal cortex of Fragile X mice}}. {The Journal of physiology}. 2012 Dec 24.
FFragile X Syndrome (FXS) is the most common form of inheritable mental retardation caused by transcriptional silencing of the Fmr1 gene resulting in the absence of fragile X mental retardation protein (FMRP). The role of this protein in neurons is complex and its absence gives rise to diverse alterations in neuronal function leading to neurological disorders including mental retardation, hyperactivity, cognitive impairment, obsessive-compulsive behavior, seizure activity, and autism. FMRP regulates mRNA translation at dendritic spines where synapses are formed, and thus, the lack of FMRP can lead to disruptions in synaptic transmission and plasticity. Many of these neurological deficits in FXS likely involve the prefrontal cortex, and in this study, we have focused on modulatory actions of dopamine (DA) in the medial prefrontal cortex (mPFC). Our data shows that dopamine produces a long-lasting enhancement of evoked inhibitory postsynaptic currents (IPSCs) mediated by D1 type receptors seen in wild type (WT) mice; however, such enhancement is absent in the Fmr1 knock-out (Fmr1 KO) mice. The facilitation of IPSCs produced by direct cAMP stimulation was unaffected in Fmr1 KO, but D1 receptor levels were reduced in these animals. Our results show significant disruption of dopaminergic modulation of synaptic transmission in the Fmr1 KO mice and this alteration in inhibitory activity may provide insight into potential targets for the rescue of deficits associated with FXS.