Novel PTEN mutations in neurodevelopmental disorders and macrocephaly
ABSTRACT Somatic mutations of the phosphatase and tensin (PTEN) gene have been frequently detected in many types of human cancer. However, germline mutations can determine multiple hamartoma syndromes and, as more recently ascertained, syndromes clinically characterized by autism associated with macrocephaly. To determine whether germline mutations of PTEN may lead to different phenotypes, we screened all the nine exons of the PTEN gene in 40 patients with neurodevelopmental disorders, with or without features of autism spectrum disorder, associated with macrocephaly. Three novel de novo missense mutations were found (p.H118P, p.Y176C, p.N276S) in two severely mentally retarded patients with autism and in a subject with neurodevelopmental disorders without autistic features. Our results provide evidence that PTEN germline mutations may sustain a more wide phenotypical spectrum than previously suggested.
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- "The same Cre-loxP approach to restricted genetic manipulations enabled the study of the brain-specific effects of genes whose ubiquitous deletion is lethal. For example, loss-offunction mutations in the phosphatase and tensin homolog (PTEN) gene are associated with a broad range of cancers and with syndromic forms of autism characterized by macrocephaly (Orrico et al. 2009). The ubiquitous homozygous deletion of Pten in rodents results in embryonic lethality, whereas haploinsufficiency produced social behavioral deficits and systemic tumors that prevent a comprehensive analysis of behavior (Page et al. 2009; Stiles et al. 2004). "
ABSTRACT: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by core differences and impairments in social behavioral functioning. There are no approved medications for improving social cognition and behavior in ASD, and the underlying mechanisms needed to discover safer, more effective medications are unclear. In this review, we diagram the basic neurocircuitry governing social behaviors in order to provide a neurobiological framework for the origins of the core social behavioral symptoms of ASD. In addition, we discuss recent technological innovations in research tools that provide unprecedented observation of cellular morphology and activity deep within the intact brain and permit the precise control of discrete brain regions and specific cell types at distinct developmental stages. The use of new technologies to reveal the neural circuits underlying social behavioral impairments associated with ASD is advancing our understanding of the brain changes underlying ASD and enabling the discovery of novel and effective therapeutic interventions.Psychopharmacology 02/2014; 231(6). DOI:10.1007/s00213-014-3464-y · 3.99 Impact Factor
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ABSTRACT: The pure Na0.5Bi4.5Ti4O15 and the V-doped Na0.5Bi4.5Ti4O15 (Na0.5Bi4.5-x/3Ti4-xVxO15 (NaBTiV-x, x=0.01, 0.03, and 0.05)) thin films were prepared by chemical solution deposition. For all samples, layered perovskite structure with a single phase and good crystalline structure was observed. And we utilized Raman spectroscopy to characterize the structural properties of the NaBTiV-x thin films. The surface was composed of fine grains without cracks in the SEM results. The NaBTiV-0.01 thin film exhibited the most outstanding electrical property among them. Remnant polarization (2Pr) was 61 μC/cm2 at room temperature and leakage current density of the NaBTiV-0.01 thin film measured at room temperature was 2.4×10−7 A/cm2 at an external electric field of 100 kV/cm. We consider that the enhanced properties may be related to reduce oxygen vacancies by doping vanadium.Current Applied Physics 10/2010; DOI:10.1016/j.cap.2010.10.014 · 2.03 Impact Factor
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ABSTRACT: We previously reported a genetic analysis of the growth-inhibitory effect caused by the overexpression of the Aspergillus oryzae rntA gene, encoding RNase T1 (Ribonuclease T1), in Saccharomyces cerevisiae. Subsequently, rns (ribonuclease T1 sensitive) mutants with mutations in the rns1 (DSL1), rns2 (UMP1), and rns3 (SEC17) genes, were identified. In the present study, rns4 (VPS32/SNF7) gene mutation was identified by complementation of tunicamycin sensitivity. While the rns4 mutant exhibited sensitivity to ambient stress conditions (200 mM CaCl(2), 1M NaCl and pH 8.0), genome-wide expression analysis revealed a similar pattern of genes up-regulated as was observed under nitrogen depletion condition by Gasch et al. [Mol. Biol. Cell 11 (2000) 4241]. Notably, the genes participating in autophagy (ATG4 and ATG8), the genes encoding a vacuolar protease (PRB1), vacuolar protease inhibitors (PAI3, PBI2 and TFS1) and YHR138c (a PBI2 homolog) were up-regulated in the rns4 mutant. Interestingly, the RNase T1*-GFP fusion protein (*inactive form) expressed in the rns4 mutant strain localized at the ER and vacuole under both stress or no-stress conditions. In contrast, the RNase T1*-GFP fusion protein expressed in the wild-type strain could not be detected under no-stress conditions, however, a stress-dependent localization of the fusion protein was observed at the vacuole. Since, the rns4 mutant exhibited a partial starvation-like response in spite of a rich ambient environment, leading to transportation of the secretory protein to the vacuole and accumulation in the endoplasmic reticulum, the present findings implicate a novel role for Rns4/Vps32 in proper response and adaptation to ambient conditions.FEMS Yeast Research 07/2005; 5(9):801-12. DOI:10.1016/j.femsyr.2005.03.003 · 2.44 Impact Factor