Variable phenotypes in individuals with grin2a sequence variants or deletionsVlaskamp, D. R. M., Callenbach, P. M. C., Rump, P., Van Pinxteren-Nagler, E., Willemsen, M. H., Gunning, B., de Geus, C., Veenstra, K. H. E., Lunsing, R. J., Dijkhuizen, T., Vos, Y. J., Brouwer, O. F. & Van Ravenswaaij-Arts, C. M. A., 1-Dec-2016, In : Epilepsia. 57, p. 126 1 p.
Research output: Contribution to journal › Meeting Abstract › Academic
Purpose: The GRIN2A gene has been associated with epilepsies ranging from benign focal childhood epilepsies to severe epileptic encephalopathies. The aim of this study was to evaluate genotypes and phenotypes in individuals with GRIN2A deletions or variants. Method: We compared genotypes and phenotypes in six newly identified patients with GRIN2A variants with those of 149 individuals with GRIN2A variants from the literature. Results: Six new patients with epilepsy, developmental and/or behavioral problems and GRIN2A deletions (n = 3), missense (n = 2) or splice-site variants (n = 1) are presented. In 125 (84%) of the 149 individuals with GRIN2A variants previously reported, a specific epilepsy syndrome was diagnosed, most often classified as Benign Epilepsy with Centro-Temporal Spikes (BECTS; n = 44) or Landau-Kleffner syndrome/ Continuous Spike-And-Waves during Slow-wave sleep (LKS/ CSWS; n = 42). Problems of speech and language development (81%), cognition (68%), motor skills (50%) or behavior (42%) were common. Missense variants were seen in 52% of the patients reported earlier, more often in individuals with BECTS (71%) compared to those with LKS/ CSWS (48%). Certain missense variants in or close to the ligand-gated ion channel domain were associated with a severe phenotype, as was also observed in two of our patients with severe epilepsy and cognitive impairment. Conclusion: Individuals with GRIN2A gene variants or deletions have an extremely variable phenotype without a clear genotype-phenotype correlation. Variants in or close to the ligand-gated ion channel can be associated with a severe phenotype.
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|Publication status||Published - 1-Dec-2016|
- endogenous compound, ligand gated ion channel, n methyl dextro aspartic acid receptor 2A, cognitive defect, controlled study, deletion mutant, diagnosis, gene deletion, genotype phenotype correlation, human, Landau Kleffner syndrome, language development, major clinical study, missense mutation, motor performance, problem behavior, slow wave sleep, speech disorder, spike