Se in these sufferers.Among the XLID-reported genes, a minimum of seven encode proteins straight linked

Se in these sufferers.Among the XLID-reported genes, a minimum of seven encode proteins straight linked to Rho GTPase-dependent signaling pathways, as regulators (FGD1, ARHGEF6, OCRL1, GDI1, OPHN1) or effectors (FMR1, PAK3). Rho GTPases are a subfamily of tiny GTP-binding proteins that regulate spine morphogenesis and synapse improvement by functioning as molecular switches, cycling amongst an active GTPbound state and an inactive GDP-bound state. In their active conformation, Rho GTPases interact with distinct effector molecules, which induce downstream signaling pathways that handle a wide range of biological processes, including actin cytoskeletal reorganization, microtubule dynamics and membrane trafficking.two These adjustments in neuronal morphology are important to the mechanisms of plasticity, mastering and memory, to ensure that inactivation of RhoGAP proteins could trigger constitutive activation of their GTPase targets, which hence could lead to XLID. The oligophrenin-1 gene (OPHN1; MIM 300127), located at Xq12, was the initial described Rho-linked ID gene, becoming CB2 Agonist manufacturer identified right after the1Department of Genetics, State University of Rio de Janeiro, Rio de Janeiro, Brazil; 2Human Genome Laboratory, VIB Center for the Biology of Disease, KU Leuven, Leuven, Belgium; 3Human Genome Laboratory, Center for Human, Genetics, KU Leuven, Leuven, Belgium; 4Clinical Genetics Service, IPPMG, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 5Laboratory of Biotechnology, Center for Biosciences and Biotechnology, State University of North Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil; 6Department of Neurology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 7Epilepsy Outpatient Section, Fluminense Federal University, Rio de Janeiro, Brazil; 8Neurology and Neurophysiology Service, State University of Rio de Janeiro, Rio de Janeiro, Brazil Correspondence: Professor CB Santos-Rebouc s, Servic de Genetica Humana, Departamento de Genetica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rua Sao Francisco Xavier, 524, PHLC–sala 501F, Maracana, Rio de Janeiro RJ 20550-013, Brazil. Tel: +55 21 23340039; Fax: +55 21 23340499; E-mail: [email protected] Received 3 Could 2013; revised 12 August 2013; accepted 16 August 2013; published online 9 OctoberOPHN1 BAR domain and intellectual disability CB Santos-Rebouc s et almolecular characterization of a X;12 balanced translocation in a female with mild ID.3,four Initially, Bcl-B Inhibitor Source mutations in this gene have been reported to be responsible for non-syndromic XLID. Nevertheless, subsequent reports suggest that OPHN1 mutations lead to a recognizable phenotype, which consists of neuroradiological hallmarks which include cerebellar hypoplasia and ventriculomegaly, too as subtle but characteristic facial functions like strabismus and deep set eyes.5,six OPHN1 is expressed at low levels in all tissues, having a particularly greater expression in neurons for the duration of development and at later stages in extremely plastic brain regions, like the olfactory bulb and hippocampus.four,7 OPHN1, localized both pre- and post-synaptically, is implicated inside the regulation of dendritic spine morphology8,9 and has a crucial role within the activity-dependent maturation and plasticity of excitatory synapses by controlling their structural and functional stability.10 Indeed, Ophn1 deficiency in mouse displays similarities towards the human phenotype and outcomes in dendritic spine immaturity, ventricular enlargement and impaired.