Polyalanine expansion of <i>ARX</i> associated with cryptogenic West syndrome

Abstract

West syndrome is an age-specific epilepsy syndrome characterized by infantile spasms, arrest of psychomotor development, and hypsarrhythmia on EEG.1 It has been divided into subgroups with known (symptomatic) or unknown (cryptogenic) etiology, with the latter comprising about 9 to 17% of patients.2 ARX is a paired-type homeobox gene on chromosome Xp22.13 that functions as a transcription factor in fetal brain and testes.3 Mutations were recently reported in patients with X-linked mental retardation, X-linked infantile spasms or West syndrome, and X-linked lissencephaly with abnormal genitalia.3-5⇓⇓ Arx-deficient male mice demonstrate deficiency of γ-aminobutyric acid (GABA)ergic inhibitory interneurons migrating from the ganglionic eminence, which should contribute to higher excitability of the brain and epilepsy.3 We suspected that mutations of ARX also cause sporadic cryptogenic West syndrome, and we detected a mutation in the coding region of ARX in one of eight patients tested (4 Japanese, 3 white, and 1 half-Asian). Following informed consent, blood was obtained and DNA extracted. PCR amplification of the coding region of ARX was performed with 50 ng of genomic DNA template. The primers …