A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation

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Item Type:	Article
Title:	A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation
Creators Name:	Motazacker, M.M., Rost, B.R., Hucho, T., Garshasbi, M., Kahrizi, K., Ullmann, R., Abedini, S.S., Nieh, S.E., Amini, S.H., Goswami, C., Tzschach, A., Jensen, L.R., Schmitz, D., Ropers, H.H., Najmabadi, H. and Kuss, A.W.
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.
Keywords:	Base Sequence, Cell Line, Complementary DNA, Consanguinity, Intellectual Disability, Kainic Acid Receptors, Molecular Models, Pedigree, Protein Conformation, Recessive Genes, Recombinant Proteins, Transfection
Source:	American Journal of Human Genetics
ISSN:	0002-9297
Publisher:	University of Chicago Press
Volume:	81
Number:	4
Page Range:	792-798
Date:	October 2007
Official Publication:	https://doi.org/10.1086/521275
PubMed:	View item in PubMed

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