title: Alexander Disease: A Novel Mutation in GFAP Leading to Epilepsia Partialis Continua.
abstract: Alexander disease is a genetically induced leukodystrophy, due to dominant mutations in the glial fibrillary acidic protein (GFAP ) gene, causing dysfunction of astrocytes. We have identified a novel GFAP mutation, associated with a novel phenotype for Alexander disease. A boy with global developmental delay and hypertonia was found to have a leukodystrophy. Genetic analysis revealed a heterozygous point mutation in exon 6 of the GFAP gene. The guanine-to-adenine change causes substitution of the normal glutamic acid codon (GAG) with a mutant lysine codon (AAG) at position 312 (E312 K mutation). At the age of 4 years, the child developed epilepsia partialis continua, consisting of unabating motor seizures involving the unilateral perioral muscles. Epilepsia partialis continua has not previously been reported in association with Alexander disease. Whether and how the E312 K mutation produces pathologic changes and clinical signs that are unique from other Alexander disease-inducing mutations in GFAP remain to be determined.
authors.affiliation: Division of Child Neurology, Department of Pediatrics, University of Iowa, Iowa City, IA, USA daniel-bonthius@uiowa.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Bonthius
authors.affiliation: Division of Child Neurology, Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
authors.forename: Bahri
authors.initials: B
authors.lastname: Karacay
mesh_terms: D038261:Alexander Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging; D002675:Child, Preschool; D017036:Epilepsia Partialis Continua / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D005904:Glial Fibrillary Acidic Protein
keywords: astrocyte; epilepsy; leukodystrophy; regional differences; seizures