ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to asevere, X-linked form of syndromal mental retardation associated with alphathalassaemia (ATR-X syndrome). In this study, we have characterised thefull-length cDNA and predicted structure of the ATRX protein. Comparativeanalysis shows that it is an entirely new member of the SNF2 subgroup of asuperfamily of proteins with similar ATPase and helicase domains. ATRXprobably acts as a regulator of gene expression. Definition of its genomicstructure enabled us to identify four novel splicing defects by screening52 affected individuals. Correlation between these and previouslyidentified mutations with variations in the ATR-X phenotype providesinsights into the pathophysiology of this disease and the normal role ofthe ATRX protein in vivo.