Complete loss of the cytoplasmic carboxyl terminus of the KCNQ2 potassium channel: a novel mutation in a large Czech pedigree with benign neonatal convulsions or other epileptic phenotypes.

PURPOSE: Benign neonatal familial convulsions (BNFCs) represent a rare epileptic disorder with autosomal dominant mode of inheritance. To date, two voltage-gated potassium (K+) channel genes, KCNQ2 and KCNQ3, have been identified in typical BNFC families. The study of new pedigrees may help detect new mutations and define genotype-phenotype correlations.

METHODS: A large Czech family was detected in which BNFC was inherited together with a broad range of various nonneonatal epileptic phenotypes. Genetic linkage study and direct mutation analysis were performed to find the disease-causing mutation.

RESULTS: In seven patients with BNFCs and no recurrence of seizures, a novel two-base-pair deletion (1369del2) was identified within the coding sequence of the KCNQ2 gene. The mutation led to a putative protein that lacked nearly all its carboxyl terminus part, which plays a critical role for the accurate expression of the functional K+ channels. Three patients with generalized tonic-clonic seizures (GTCSs), all without any history of BNFCs, also displayed 1369del2. Three other patients with other idiopathic epileptic phenotypes did not have the mutation.

CONCLUSIONS: A novel 2-bp deletion within the coding sequence of the potassium channel KCNQ2 gene was detected in patients from a large and heterogeneous family with BNFCs or non-BNFC seizures.