Referenced in: none

Automatically associated channels: Kv7.2 , Kv7.3

Title: A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation.

Authors: R Borgatti, C Zucca, A Cavallini, M Ferrario, C Panzeri, P Castaldo, M V Soldovieri, C Baschirotto, N Bresolin, B Dalla Bernardina, M Taglialatela, M T Bassi

Journal, date & volume: Neurology, 2004 Jul 13 , 63, 57-65

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15249611

Abstract
Benign familial neonatal convulsion (BFNC) is a rare autosomal dominant disorder caused by mutations in two genes, KCNQ2 and KCNQ3, encoding for potassium channel subunits underlying the M-current. This current limits neuronal hyperexcitability by causing spike-frequency adaptation.The authors describe a BFNC family with four affected members: two of them exhibit BFNC only while the other two, in addition to BFNC, present either with a severe epileptic encephalopathy or with focal seizures and mental retardation.All affected members of this family carry a novel missense mutation in the KCNQ2 gene (K526N), disrupting the tri-dimensional conformation of a C-terminal region of the channel subunit involved in accessory protein binding. When heterologously expressed in CHO cells, potassium channels containing mutant subunits in homomeric or heteromeric configuration with wild-type KCNQ2 and KCNQ3 subunits exhibit an altered voltage-dependence of activation, without changes in intracellular trafficking and plasma membrane expression.The KCNQ2 K526N mutation may affect M-channel function by disrupting the complex biochemical signaling involving KCNQ2 C-terminus. Genetic rather than acquired factors may be involved in the pathophysiology of the phenotypic variability of the neurologic symptoms associated with BFNC in the described family.