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.