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

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dc.contributor.authorStromme, P.
dc.contributor.authorMangelsdorf, M.
dc.contributor.authorShaw, M.
dc.contributor.authorLower, K.
dc.contributor.authorLewis, S.
dc.contributor.authorBruyere, H.
dc.contributor.authorLutcherath, V.
dc.contributor.authorGedeon, A.
dc.contributor.authorWallace, R.
dc.contributor.authorScheffer, I.
dc.contributor.authorTurner, G.
dc.contributor.authorPartington, M.
dc.contributor.authorFrints, S.
dc.contributor.authorFryns, J.
dc.contributor.authorSutherland, G.
dc.contributor.authorMulley, J.
dc.contributor.authorGecz, J.
dc.date.issued2002
dc.description.abstractMental 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.
dc.description.statementofresponsibilityPetter 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
dc.identifier.citationNature Genetics, 2002; 30(4):441-445
dc.identifier.doi10.1038/ng862
dc.identifier.issn1061-4036
dc.identifier.issn1546-1718
dc.identifier.orcidShaw, M. [0000-0002-5060-190X]
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]
dc.identifier.urihttp://hdl.handle.net/2440/28173
dc.language.isoen
dc.publisherNature America Inc
dc.source.urihttps://doi.org/10.1038/ng862
dc.subjectX Chromosome
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectEpilepsy
dc.subjectDrosophila Proteins
dc.subjectPoly A
dc.subjectNucleic Acid Hybridization
dc.subjectPedigree
dc.subjectTranscription, Genetic
dc.subjectAmino Acid Sequence
dc.subjectSequence Homology, Amino Acid
dc.subjectTissue Distribution
dc.subjectHaplotypes
dc.subjectMutation
dc.subjectMutation, Missense
dc.subjectModels, Genetic
dc.subjectMolecular Sequence Data
dc.subjectFamily Health
dc.subjectFemale
dc.subjectMale
dc.subjectIntellectual Disability
dc.titleMutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy
dc.typeJournal article
pubs.publication-statusPublished

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