, 644?51; doi:ten.1038/ejhg.2013.216; published on line 9 October 2013 Key phrases: X-linked intellectual disability; Rho GTPase; Oligophrenin-1; BAR domain; cerebellar hypoplasia; hippocampusINTRODUCTION Intellectual disability (ID), formerly referred to as mental retardation (MR), is defined by a non-progressive reduction in cognitive skills, which manifests before the age of 18 years and impacts two? from the general population.1 The etiopathological components for ID are highly heterogeneous, like environmental elements too as established genetic causes, several of which represent X-chromosome-linked conditions (XLID). To date, more than 100 XLID genes have been identified (http://ggc.org/research/molecular-studies/xlid.html), while mutation screens and linkage information strongly suggest that a lot of far more novel genes or mutational mechanisms remain elusive. Hence, the important percentage of non-syndromic XLID instances, in which no extra distinguishing capabilities are present, turn the diagnostic approach into a terrific challenge with a higher rate of underdiagnoses. As a consequence, endophenotyping, that is certainly, the identification of subtle but characteristic clinical capabilities, becomes important in the look for the underlying genetic lead to in these sufferers.Among the XLID-reported genes, no less than seven encode proteins directly linked to Rho GTPase-dependent signaling pathways, as regulators (FGD1, ARHGEF6, OCRL1, GDI1, OPHN1) or effectors (FMR1, PAK3). Rho GTPases are a subfamily of smaller GTP-binding proteins that regulate spine morphogenesis and synapse development 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 particular effector molecules, which induce downstream signaling pathways that manage a wide range of biological processes, including actin cytoskeletal reorganization, microtubule dynamics and membrane trafficking.1479-58-9 supplier two These alterations in neuronal morphology are critical to the mechanisms of plasticity, mastering and memory, to ensure that inactivation of RhoGAP proteins might bring about constitutive activation of their GTPase targets, which thus could lead to XLID. The oligophrenin-1 gene (OPHN1; MIM 300127), located at Xq12, was the first described Rho-linked ID gene, getting 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.tert-Butyl oct-7-yn-1-ylcarbamate In stock Tel: +55 21 23340039; Fax: +55 21 23340499; E-mail: cbs@alternex.PMID:33626958 br Received 3 May possibly 2013; revised 12 August.