Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy

Petter Strømme, Marie E. Mangelsdorf, Marie A. Shaw, Karen M. Lower, Suzanne M.E. Lewis, Helene Bruyere, Viggo Lütcherath, Ági K. Gedeon, Robyn H. Wallace, Ingrid E. Scheffer, Gillian Turner, Michael Partington, Suzanna G.M. Frints, Jean Pierre Fryns, Grant R. Sutherland, John C. Mulley, Jozef Gécz

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384 Citations (Scopus)


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 1 . At least eight autosomal genes involved in idiopathic epilepsy have been identified 2 , 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 polyalanine3 and polyglutamine4 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.

Original languageEnglish
Pages (from-to)441-445
Number of pages5
JournalNature Genetics
Issue number4
Publication statusPublished - 1 Jan 2002
Externally publishedYes


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