GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction.
Epileptic encephalopathies are severe brain disorders with the epileptic component contributing to the worsening of cognitive and behavioral manifestations. Acquired epileptic aphasia (Landau-Kleffner syndrome, LKS) and continuous spike and waves during slow-wave sleep syndrome (CSWSS) represent rare and closely related childhood focal epileptic encephalopathies of unknown etiology. They show electroclinical overlap with rolandic epilepsy (the most frequent childhood focal epilepsy) and can be viewed as different clinical expressions of a single pathological entity situated at the crossroads of epileptic, speech, language, cognitive and behavioral disorders. Here we demonstrate that about 20% of cases of LKS, CSWSS and electroclinically atypical rolandic epilepsy often associated with speech impairment can have a genetic origin sustained by de novo or inherited mutations in the GRIN2A gene (encoding the N-methyl-D-aspartate (NMDA) glutamate receptor α2 subunit, GluN2A). The identification of GRIN2A as a major gene for these epileptic encephalopathies provides crucial insights into the underlying pathophysiology.
Department of Genetics, University Hospitals of Lyon, Lyon, France.
Gaetan
G
Lesca
Gabrielle
G
Rudolf
Nadine
N
Bruneau
Natalia
N
Lozovaya
Audrey
A
Labalme
Nadia
N
Boutry-Kryza
Manal
M
Salmi
Timur
T
Tsintsadze
Laura
L
Addis
Jacques
J
Motte
Sukhvir
S
Wright
Vera
V
Tsintsadze
Anne
A
Michel
Diane
D
Doummar
Karine
K
Lascelles
Lisa
L
Strug
Patrick
P
Waters
Julitta
J
de Bellescize
Pascal
P
Vrielynck
Anne
A
de Saint Martin
Dorothee
D
Ville
Philippe
P
Ryvlin
Alexis
A
Arzimanoglou
Edouard
E
Hirsch
Angela
A
Vincent
Deb
D
Pal
Nail
N
Burnashev
Damien
D
Sanlaville
Pierre
P
Szepetowski
D019943:Amino Acid Substitution; D002460:Cell Line; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D018887:Landau-Kleffner Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
D016194:Receptors, N-Methyl-D-Aspartate