A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation.
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.
Motazacker
Mohammad Mahdi
MM
Max Planck Institute for Molecular Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.
Rost
Benjamin Rainer
BR
Hucho
Tim
T
Garshasbi
Masoud
M
Kahrizi
Kimia
K
Ullmann
Reinhard
R
Abedini
Seyedeh Sedigheh
SS
Nieh
Sahar Esmaeeli
SE
Amini
Saeid Hosseini
SH
Goswami
Chandan
C
Tzschach
Andreas
A
Jensen
Lars Riff
LR
Schmitz
Dietmar
D
Ropers
Hans Hilger
HH
Najmabadi
Hossein
H
Kuss
Andreas Walter
AW
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
D018076:DNA, Complementary; D018092:Kainic Acid Receptors; D011994:Recombinant Proteins; D000097806:GluK2 Kainate Receptor