title: Mutations in the chromatin-associated protein ATRX.
abstract: 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.
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. richard.gibbons@imm.ox.ac.uk
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gibbons
authors.forename: Takahito
authors.initials: T
authors.lastname: Wada
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Fisher
authors.forename: Nicola
authors.initials: N
authors.lastname: Malik
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Mitson
authors.forename: David P
authors.initials: DP
authors.lastname: Steensma
authors.forename: Alan
authors.initials: A
authors.lastname: Fryer
authors.forename: David R
authors.initials: DR
authors.lastname: Goudie
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
authors.forename: Joanne
authors.initials: J
authors.lastname: Traeger-Synodinos
mesh_terms: D001483:Base Sequence; D042002:Chromatin Assembly and Disassembly; D018389:Codon, Nonsense; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D017434:Protein Structure, Tertiary; D000075924:X-linked Nuclear Protein; D017085:alpha-Thalassemia / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D009687:Nuclear Proteins; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein