title: A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation.
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.
authors.affiliation: Max Planck Institute for Molecular Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Motazacker
authors.forename: Benjamin Rainer
authors.initials: BR
authors.lastname: Rost
authors.forename: Tim
authors.initials: T
authors.lastname: Hucho
authors.forename: Masoud
authors.initials: M
authors.lastname: Garshasbi
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.forename: Seyedeh Sedigheh
authors.initials: SS
authors.lastname: Abedini
authors.forename: Sahar Esmaeeli
authors.initials: SE
authors.lastname: Nieh
authors.forename: Saeid Hosseini
authors.initials: SH
authors.lastname: Amini
authors.forename: Chandan
authors.initials: C
authors.lastname: Goswami
authors.forename: Andreas
authors.initials: A
authors.lastname: Tzschach
authors.forename: Lars Riff
authors.initials: LR
authors.lastname: Jensen
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
authors.forename: Hans Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.forename: Andreas Walter
authors.initials: AW
authors.lastname: Kuss
mesh_terms: D000328:Adult; D001483:Base Sequence; D002460:Cell Line; D003241:Consanguinity; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism; D007558:Italy; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D010375:Pedigree; D011487:Protein Conformation; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000097806:GluK2 Kainate Receptor
chemical_list: D018076:DNA, Complementary; D018092:Kainic Acid Receptors; D011994:Recombinant Proteins; D000097806:GluK2 Kainate Receptor