title: ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome.
abstract: It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Picketts
authors.forename: D R
authors.initials: DR
authors.lastname: Higgs
authors.forename: S
authors.initials: S
authors.lastname: Bachoo
authors.forename: D J
authors.initials: DJ
authors.lastname: Blake
authors.forename: O W
authors.initials: OW
authors.lastname: Quarrell
authors.forename: R J
authors.initials: RJ
authors.lastname: Gibbons
mesh_terms: D000595:Amino Acid Sequence; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D000075924:X-linked Nuclear Protein; D017085:alpha-Thalassemia / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C499336:SMARCA1 protein, human; C084011:SMARCA2 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein