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

Strømme, Petter, Mangelsdorf, Marie E., Shaw, Marie A., Lower, Karen M., Lewis, Suzanne M. E., Bruyere, Helene, Lütcherath, Viggo, Gedeon, Ági K., Wallace, Robyn H., Scheffer, Ingrid E., Turner, Gillian, Partington, Michael, Frints, Suzanna G. M., Fryns, Jean-Pierre, Sutherland, Grant R., Mulley, John C. and Gécz, Jozef (2002) Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nature Genetics, 30 4: 441-445. doi:10.1038/ng862

Author Strømme, Petter
Mangelsdorf, Marie E.
Shaw, Marie A.
Lower, Karen M.
Lewis, Suzanne M. E.
Bruyere, Helene
Lütcherath, Viggo
Gedeon, Ági K.
Wallace, Robyn H.
Scheffer, Ingrid E.
Turner, Gillian
Partington, Michael
Frints, Suzanna G. M.
Fryns, Jean-Pierre
Sutherland, Grant R.
Mulley, John C.
Gécz, Jozef
Title Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
Publication date 2002-01-01
Year available 2002
Sub-type Article (original research)
DOI 10.1038/ng862
Open Access Status
Volume 30
Issue 4
Start page 441
End page 445
Total pages 5
Place of publication NY
Publisher Nature Publishing Group
Language eng
Subject 0604 Genetics
11 Medical and Health Sciences
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(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 polyalanine(3) and polyglutamine(4) 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.
Keyword Genetics & Heredity
Oculopharyngeal Muscular-dystrophy
Infantile Spasms
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 313 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 335 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 03:37:59 EST