title: Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy.
abstract: Mental retardation and epilepsy often occur together. They are both heterogeneous conditions with acquired and genetic causes. Where causes are primarily genetic, major advances have been made in unraveling their molecular basis. The human X chromosome alone is estimated to harbor more than 100 genes that, when mutated, cause mental retardation. At least eight autosomal genes involved in idiopathic epilepsy have been identified, and many more have been implicated in conditions where epilepsy is a feature. We have identified mutations in an X chromosome-linked, Aristaless-related, homeobox gene (ARX), in nine families with mental retardation (syndromic and nonspecific), various forms of epilepsy, including infantile spasms and myoclonic seizures, and dystonia. Two recurrent mutations, present in seven families, result in expansion of polyalanine tracts of the ARX protein. These probably cause protein aggregation, similar to other polyalanine and polyglutamine disorders. In addition, we have identified a missense mutation within the ARX homeodomain and a truncation mutation. Thus, it would seem that mutation of ARX is a major contributor to X-linked mental retardation and epilepsy.
authors.affiliation: Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia.
authors.forename: Petter
authors.initials: P
authors.lastname: Strømme
authors.forename: Marie E
authors.initials: ME
authors.lastname: Mangelsdorf
authors.forename: Marie A
authors.initials: MA
authors.lastname: Shaw
authors.forename: Karen M
authors.initials: KM
authors.lastname: Lower
authors.forename: Suzanne M E
authors.initials: SM
authors.lastname: Lewis
authors.forename: Helene
authors.initials: H
authors.lastname: Bruyere
authors.forename: Viggo
authors.initials: V
authors.lastname: Lütcherath
authors.forename: Agi K
authors.initials: AK
authors.lastname: Gedeon
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Wallace
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Gillian
authors.initials: G
authors.lastname: Turner
authors.forename: Michael
authors.initials: M
authors.lastname: Partington
authors.forename: Suzanna G M
authors.initials: SG
authors.lastname: Frints
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Grant R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Jozef
authors.initials: J
authors.lastname: Gécz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics*; D005192:Family Health; D005260:Female; D006239:Haplotypes; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D011061:Poly A / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014960:X Chromosome
chemical_list: D029721:Drosophila Proteins; C079410:al protein, Drosophila; D011061:Poly A