We found suggestive linkage of the BFNC phenotype to the 20q13-EBN1 locus (lod score, 2.03) and an intronic mutation IVS14-6 C>A in KCNQ2 segregating with the trait in all affected members, but absent in 100 unrelated control subjects.
Benign childhood epilepsy with centrotemporal spikes and electroencephalography trait are not linked to EBN1 and EBN2 of benign neonatal familial convulsions.
Linkage is established for three generalized syndromes: the EBN1 and EBN2 genes for benign familial neonatal convulsions (BFNC) map to chromosomes 20q and 8q (refs 2-5), the EPM1 gene for Unverricht-Lundborg disease maps to 21q (ref.
Here we report on a second BFNC family in which linkage to the EBN1 locus on chromosome 20q was excluded, confirming the genetic heterogeneity of this disorder.
Identification of CHRNA4 as the defective gene in 20q-BFNC represents the first example of a human idiopathic epilepsy caused by a mutation directly affecting a neurotransmitter receptor in the central nervous system.