Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2.
Mutations in the voltage gated K(+)-channel gene KCNQ2 are known to cause benign familial neonatal convulsions (BFNC), which are characterized by a benign course, spontaneous remission and normal psychomotor development. Most KCNQ2 mutations can be predicted to truncate the protein. Only a few amino acid exchanges have been found, and their localization was restricted to either the pore region or the fourth or sixth transmembrane region (TM). We have now identified the first KCNQ2 mutation located within TM5, affecting a highly conserved serine in amino acid position 247 of the predicted protein. The clinical history of the two affected family members is not compatible with typical BFNC. The poor outcome in the index patient raises the question if at least some KCNQ2 mutations might increase the risk to develop therapy-resistant epilepsy. Additional studies are needed to evaluate the possibility of a causal relationship between KCNQ2 mutations and severe early infantile epilepsy.
Dedek
Karin
K
Zentrum für Molekulare Neurobiologie (ZMNH), University Hamburg, Hamburg, Germany.
Fusco
Lucia
L
Teloy
Nicole
N
Steinlein
Ortrud K
OK
D000328:Adult; D019943:Amino Acid Substitution; D000818:Animals; D004247:DNA / Q000235:genetics; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D020936:Epilepsy, Benign Neonatal / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007558:Italy; D051658:KCNQ2 Potassium Channel; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D014982:Xenopus laevis
D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D004247:DNA