ARX spectrum disorders: Making inroads into the molecular pathology

Cheryl Shoubridge, Tod Fullston, Jozef Gécz

Research output: Contribution to journalReview articlepeer-review

129 Citations (Scopus)

Abstract

The Aristaless-related homeobox gene (ARX) is one of the most frequently mutated genes in a spectrum of X-chromosome phenotypes with intellectual disability (ID) as their cardinal feature. To date, close to 100 families and isolated cases have been reported to carry 44 different mutations, the majority of these (59%) being a result of polyalanine tract expansions. At least 10 well-defined clinical entities, including Ohtahara, Partington, and Proud syndromes, X-linked infantile spasms, X-linked lissencephaly with ambiguous genitalia, X-linked myoclonic epilepsy and nonsyndromic intellectual disability have been ascertained from among the patients with ARX mutations. The striking intra- and interfamilial pleiotropy together with genetic heterogeneity (same clinical entities associated with different ARX mutations) are becoming a hallmark of ARX mutations. Although males are predominantly affected, some mutations associated with malformation phenotypes in males also show a phenotype in carrier females. Recent progress in the study of the effect of ARX mutations through sophisticated animal (mice) and cellular models begins to provide crucial insights into the molecular function of ARX and associated molecular pathology, thus guiding future inquiries into therapeutic interventions.

Original languageEnglish
Pages (from-to)889-900
Number of pages12
JournalHuman Mutation
Volume31
Issue number8
DOIs
Publication statusPublished or Issued - 1 Aug 2010

Keywords

  • ARX
  • Aristaless-related homeobox gene
  • Expanded polyalanine
  • Homeodomain transcription factor
  • Intellectual disability
  • Seizures

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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