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Brain Advance Access originally published online on October 8, 2003
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Brain, Vol. 126, No. 12, 2726-2737, December 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg286

KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum

Nanda A. Singh1, Peter Westenskow2, Carole Charlier4, Chris Pappas1, Jonathan Leslie1, Jessica Dillon2,5 The BFNC Physician Consortium, V. Elving Anderson3, Michael C. Sanguinetti2 and Mark F. Leppert1

1 Department of Human Genetics and 2 Department of Physiology, University of Utah, Salt Lake City, Utah, and 3 Division of Epidemiology, University of Minnesota, Minneapolis, Minnesota, USA, 4 Department of Genetics, Faculty of Veterinary Medicine, University of Liege, Liege, Belgium. 5 Names and addresses of the Consortium members are listed in the Acknowledgements.

Correspondence to: Nanda A. Singh, PhD, Eccles Institute of Human Genetics, 15N 2030E, Rm 2100, University of Utah, Salt Lake City, UT 84112, USA E-mail: nandas{at}genetics.utah.edu

Benign familial neonatal convulsions (BFNC) is a rare autosomal dominant generalized epilepsy of the newborn infant. Seizures occur repeatedly in the first days of life and remit by approximately 4 months of age. Previously our laboratory cloned two novel potassium channel genes, KCNQ2 and KCNQ3, and showed that they are mutated in patients with BFNC. In this report, we characterize the breakpoints of a previously reported interstitial deletion in the KCNQ2 gene and show that only KCNQ2 is deleted. We identify 11 novel mutations in KCNQ2 and one novel mutation in the KCNQ3 potassium channel genes. In one family, the phenotype extends beyond neonatal seizures and includes rolandic seizures, and a subset of families has onset of seizures in infancy. In the Xenopus oocyte expression system, we characterize five KCNQ2 and one KCNQ3 disease-causing mutations. These mutations cause a variable loss of function, and selective effects on the biophysical properties of KCNQ2/KCNQ3 heteromultimeric channels. We report here the first dominant negative mutation in KCNQ2 that has a phenotype of neonatal seizures without permanent clinical CNS impairment.


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