1p34.3 deletion involving GRIK3: Further clinical implication of GRIK family glutamate receptors in the pathogenesis of developmental delay.
A growing body of evidence suggests an association between microdeletion/microduplication and schizophrenia/intellectual disability. Abnormal neurogenesis and neurotransmission have been implicated in the pathogenesis of these neuropsychiatric and neurodevelopmental disorders. The kainate/AMPA-type ionotropic glutamate receptor (GRIK = glutamate receptor, ionotropic, kainate) plays a critical role in synaptic potentiation, which is an essential process for learning and memory. Among the five known GRIK family members, haploinsufficiency of GRIK1, GRIK2, and GRIK4 are known to cause developmental delay, whereas the roles of GRIK3 and GRIK5 remain unknown. Herein, we report on a girl who presented with a severe developmental delay predominantly affecting her language and fine motor skills. She had a 2.6-Mb microdeletion in 1p34.3 involving GRIK3, which encodes a principal subunit of the kainate-type ionotropic glutamate receptor. Given its strong expression pattern in the central nervous system and the biological function of GRIK3 in presynaptic neurotransmission, the haploinsufficiency of GRIK3 is likely to be responsible for the severe developmental delay in the proposita. A review of genetic alterations and the phenotypic effects of all the GRIK family members support this hypothesis. The current observation of a microdeletion involving GRIK3, a kainate-type ionotropic glutamate receptor subunit, and the neurodevelopmental manifestation in the absence of major dysmorphism provides further clinical implication of the possible role of GRIK family glutamate receptors in the pathogenesis of developmental delay.
Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
Toshiki
T
Takenouchi
Noriko
N
Hashida
Chiharu
C
Torii
Rika
R
Kosaki
Takao
T
Takahashi
Kenjiro
K
Kosaki
D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D018092:Kainic Acid Receptors / Q000235:genetics*; D000097808:GluK3 Kainate Receptor
D018092:Kainic Acid Receptors; D000097808:GluK3 Kainate Receptor
GRIK3; developmental delay; glutamate receptor