Expanding the spectrum of Grik2 mutations: intellectual disability, behavioural disorder, epilepsy and dystonia

Interaction among GRIK2 gene on epilepsy susceptibility in Chinese children

“…But we did not identify any relationship between rs9390754 and rs2235076 within GRIK2 gene with epilepsy risk in this population. Although our research was not the first case‐control study for the relationship between SNP within GRIK2 gene and epilepsy risk, however these previous studies were limited to conclude a consistent result for this relationship. Previously, no correlation between GRIK1 polymorphisms and epilepsy was found .…”

“…Manuel et al used genome‐wide association analysis (GWAS) to find that the gene was associated with obsessive‐compulsive neurological disorders. Cordoba et al found that abnormal mutation of GRIK2 gene may lead to mental retardation and other related diseases. Lee et al found that there was no correlation between the repeat mutation of triple‐based TAA of GRIK2 gene and the age of Huntington's chorea.…”

“…Wang et al also suggested that GRIK2 gene was a candidate gene for epilepsy. Previously, some studies concluded that GRIK2 gene causes neurodevelopmental deficits and intellectual disability (ID) . GRIK2 was proposed as the genetic cause of isolated moderate to severe ID in an Iranian family .…”

“…GRIK2 gene is located in the 6q21 region, which is the susceptibility linkage region of many reported mental disorders. Some studies have reported that GRIK2 gene was associated with obsessive‐compulsive neurological disorders, mental retardation, Huntington's chorea, and onset of autism spectrum disorder . Animal experiment also suggested that GRIK2 gene was related to the maintenance and control of epileptic seizures .…”

Autism and intellectual disability in a patient with two microdeletions in 6q16: a contiguous gene deletion syndrome?

“…16 FBXL4/605654 mtDNA depletion syndrome (infantile encephalomyopathic type)Coding for a member of the F-Box family (targeting substrates for degradation of cellular regulatory proteins)Maintenance of mtDNA%HI score 10.28[31–33]recessive6 POU3F2/600494 None describedPOU domain transcription factor predominantly expressed in the CNS.Likely playing an important role in mammalian neurogenesis and neuronal migration in the neocortex, positive regulator of Schwann cell development, downstream target of SIM1 %HI score 15.18[15–17, 34]Unknown6 PRDM13/616741 North Carolina Macular Dystrophy (NCMD), no other neurologic phenotype describedPrdm transcription factor, neural specific direct target of Ptf1a, controlling balance of inhibitory and excitatory neurons in somatosensory circuits during neuronal development,Required to produce the right number of pax2+ neurons in the dorsal spinal cord by repressing excitatory cell fate%HI score 56.20[25, 35, 36]dominant for NCMD, otherwise unknown6 CCNC/123838 None describedMember of the cyclin family,Protein kinase in the RNA polymerase II complex, cell cycle regulator%HI score 2.44[30, 37]Unknown, Protein involved in pathogenesis of tumour development and Alzheimer disease6 COQ3/605196 None describedEncodes an O-Methyltransferase, involved in two steps of Ubiquinone (Coenzyme Q10) biosynthesis%HI score 40.90[29, 38]UnknownDeletion Nr. 26 GRIK2/138244 Intellectual disability; ASD; behavioural disorder, epilepsy, dystoniaEncodes for the glutamate receptor 6, excitatory neurotransmission in the brain%HI score 2.34[5, 6, 9, 18, 22, 39]recessive; susceptibility geneDeletion 1 of our patient encompasses 9 genes, including FBXL4, POU3F2, CCNC, USP45, PNISR, FAXC, TSTD3, COQ3 and PRDM13 . Deletion 2 partially encompasses GRIK2 (details see text) .…”