Further evidence for GRIN2B mutation as the cause of severe epileptic encephalopathy.
Epileptic encephalopathies (EE) include a range of severe epilepsies in which intractable seizures or severe sub-clinical epileptiform activity are accompanied by impairment of motor and cognitive functions. Mutations in several genes including ion channels and other genes whose function is not completely understood have been associated to some EE. In this report, we provide a detailed clinical description of a sporadic male patient with early-onset epilepsy and epileptic encephalopathy in whom we performed complete exome sequencing (WES) and identified a GRIN2B mutation. The GRIN2B splicing mutation in intron 10 (c.2011-1G>A) was revealed in a WES study. The result was confirmed by Sanger sequencing. No mutation was found in both parents. Our finding confirms that early-onset EE may be caused not only by gain-of-function variants but also by splice site mutations-in particular those affecting the splice acceptor site of the 10th intron of the GRIN2B gene. © 2016 Wiley Periodicals, Inc.
Department of Paediatrics, Wroclaw Medical University, Wroclaw, Poland.
Robert
R
Smigiel
Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
Grazyna
G
Kostrzewa
Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
Joanna
J
Kosinska
Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
Agnieszka
A
Pollak
World Hearing Center, Institute of Physiology and Pathology of Hearing, Warsaw, Poland.
Piotr
P
Stawinski
Department of Genetics, Wroclaw Medical University, Wroclaw, Poland.
Elzbieta
E
Szmida
Department of Paediatrics, Wroclaw Medical University, Wroclaw, Poland.
Michal
M
Bloch
Department of Child Psychiatry, Warsaw Medical University, Warsaw, Poland.|Department of Experimental and Clinical Neuropathology, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
Krystyna
K
Szymanska
Department of Genetics, Wroclaw Medical University, Wroclaw, Poland.
Pawel
P
Karpinski
Department of Genetics, Wroclaw Medical University, Wroclaw, Poland.
Maria M
MM
Sasiadek
Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
Rafal
R
Ploski
D015415:Biomarkers; D002648:Child; D002872:Chromosome Deletion; D002894:Chromosomes, Human, Pair 4; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis* / Q000235:genetics*; D059472:Exome; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D059906:Neuroimaging; D010641:Phenotype; D010808:Physical Examination; D022821:RNA Splice Sites; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
D015415:Biomarkers; C121001:NR2B NMDA receptor; D022821:RNA Splice Sites; D016194:Receptors, N-Methyl-D-Aspartate
GRIN2B; epilepsy; epileptic encephalopathy; severe intellectual disability; speech delay; splicing mutation