Mutations in the chromatin-associated protein ATRX

Hum Mutat. 2008 Jun;29(6):796-802. doi: 10.1002/humu.20734.


ATRX belongs to the SNF2 family of proteins, many of which have been demonstrated to have chromatin remodeling activity. Constitution mutations in the X-encoded gene give rise to alpha thalassemia mental retardation (ATR-X) syndrome and a variety of related conditions that are often associated with profound developmental delay, facial dysmorphism, genital abnormalities, and alpha thalassemia. Acquired mutations in ATRX are observed in the preleukemic condition alpha thalassemia myelodysplastic syndrome (ATMDS). Mutations in ATRX have been shown to perturb gene expression and DNA methylation. This is a comprehensive report of 127 mutations including 32 reported here for the first time. Missense mutations are shown to cluster in the two main functional domains. The truncating mutations appear to be "rescued" to some degree and so it appears likely that most if not all constitutional ATRX mutations are hypomorphs.

MeSH terms

  • Base Sequence
  • Chromatin Assembly and Disassembly*
  • Codon, Nonsense
  • DNA Helicases / chemistry
  • DNA Helicases / genetics*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Mental Retardation, X-Linked / genetics*
  • Models, Molecular
  • Mutation*
  • Mutation, Missense
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics*
  • Protein Structure, Tertiary
  • X-linked Nuclear Protein
  • alpha-Thalassemia / genetics*


  • Codon, Nonsense
  • Nuclear Proteins
  • DNA Helicases
  • ATRX protein, human
  • X-linked Nuclear Protein