Infantile seizures and other epileptic phenotypes in a Chinese family with a missense mutation of KCNQ2.

INTRODUCTION: Benign familial infantile seizures (BFIS) is a form of idiopathic epilepsy characterized by clusters of afebrile seizures occurring around the sixth month of life and a favorable outcome. Linkage analysis has revealed that three chromosomal segments, 19q12-q13.1, 16p12-q12, and 2q23-31, are linked to this disorder. SUBJECTS AND METHODS: We report here a large Chinese family in which all 17 affected members had had infantile seizures with onset at age 2-4 months, with two of these also manifesting seizures later in life accompanied with either choreoathetosis or myokymia. Linkage analysis in this family confirmed a previous report of genetic heterogeneity in BFIS - since linkage was excluded at the above-mentioned known BFIS loci - and suggested a possible linkage to the KCNQ2 gene, which is believed to be a voltage gated potassium channel gene responsible for benign familial neonatal seizures (BFNS). RESULTS AND DISCUSSION: Sequencing of the KCNQ2 gene revealed that all 17 affected family members carried a heterozygous Gly-to-Val (G271V) mutation in the conserved pore region that resulted from a guanine-to-thymine transition in exon 5 of KCNQ2. The same mutation with a comparable localization in the KCNQ3 (G310V) gene has been found in BFNS patients. The same conserved amino acid was also found to be mutated in the KCNQ1 gene in a family with Long QT Syndrome.