A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome)

Early infantile epileptic encephalopathy with suppression-burst pattern (EIEE) is one of the most severe and earliest forms of epilepsx,, often evolving into West syndrome; however, the pathogenesis of EIEE remains unclear. ARX is a crucial,gene for the development of interneurons in the fetal brain, and a polyalanine expansion mutation of APX causes mental retardation and seizures, including those of West syndrome, in males. We screened the ARX mutation and found a hemizygous, de novo, 33-bp duplication in exon 2, 298_330dupGCGGCA(GCG)(9), in two of three unrelated male patients with ElEE. This mutation is thought to expand the original 16 alanine residues to 27 alanine residues (A110_A111 insAAAAAAAAAAA) in the first polyalanine tract of the ARX protein. Although ElEE is mainly associated with brain malformations, ARX is the first gene found to be responsible for idiopathic EIEE. Our observation that ElEE had a longer expansion of the polyalanine tract than is seen in West syndrome is consistent with the findings of earlier onset and more-severe phenotypes in ElEE than in West syndrome.