ATR-X (X-linked α-thalassemia/intellectual disability) syndrome (MIM: #301040) is an X-linked intellectual disability syndrome caused by loss-of-function variants of the ATRX gene (MIM: *300032), encoding an ATP-dependent chromatin remodeling protein, ATRX, located on the X chromosome, Xq21.2.
It is estimated that one in 58,000 - 73,000 newborn boys are affected each year in Japan. The incidence may vary in other countries.
It occurs in males and is characterised by severe psychomotor developmental delay, α-thalassemia (HbH disease), distinctive facial features, genital abnormalities, skeletal abnormalities, and unique behavioural and postural abnormalities.
The protein ATRX, encoded by the ATRX gene, is a chromatin remodeling factor and is believed to be involved in the regulation of multiple gene expressions. Mutations in the ATRX gene are thought to disrupt epigenetic control mechanisms, leading to abnormal gene expression and resulting in a variety of symptoms.
Recently, it has been revealed that the ATRX protein binds to special genomic structures (G-quadruplex: G4, guanine quadruplex) and is involved in the regulation of gene expression in nearby genes. Currently, research is underway to develop therapeutic agents based on this mechanism.
ATRX