1. A Defect in the Ionotropic Glutamate Receptor 6 Gene (GRIK2) Is Associated with Autosomal Recessive Mental Retardation
- Author
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Hossein Najmabadi, Andreas Tzschach, Lars Riff Jensen, Saeid Hosseini Amini, Chandan Goswami, Kimia Kahrizi, Sahar Esmaeeli Nieh, Tim Hucho, Andreas W. Kuss, Hans-Hilger Ropers, M. Mahdi Motazacker, Seyedeh Sedigheh Abedini, Reinhard Ullmann, Benjamin R. Rost, Masoud Garshasbi, Dietmar Schmitz, and Experimental Vascular Medicine
- Subjects
Adult ,Male ,Models, Molecular ,DNA, Complementary ,Protein Conformation ,Genes, Recessive ,Kainate receptor ,Biology ,Transfection ,medicine.disease_cause ,Cell Line ,Gene product ,Consanguinity ,Receptors, Kainic Acid ,GRIK2 ,Intellectual Disability ,Report ,Genetics ,medicine ,Humans ,Genetics(clinical) ,Genetics (clinical) ,Loss function ,Mutation ,Base Sequence ,Middle Aged ,Recombinant Proteins ,Pedigree ,Transmembrane domain ,Italy ,biology.protein ,Ionotropic glutamate receptor ,Female ,Ionotropic effect - Abstract
Nonsyndromic mental retardation is one of the most important unresolved problems in genetic health care. Autosomal forms are far more common than X-linked forms, but, in contrast to the latter, they are still largely unexplored. Here, we report a complex mutation in the ionotropic glutamate receptor 6 gene (GRIK2, also called "GLUR6") that cosegregates with moderate-to-severe nonsyndromic autosomal recessive mental retardation in a large, consanguineous Iranian family. The predicted gene product lacks the first ligand-binding domain, the adjacent transmembrane domain, and the putative pore loop, suggesting a complete loss of function of the GLU(K6) protein, which is supported by electrophysiological data. This finding provides the first proof that GLU(K6) is indispensable for higher brain functions in humans, and future studies of this and other ionotropic kainate receptors will shed more light on the pathophysiology of mental retardation.
- Published
- 2007