ATR-X syndrome (MIM: #301040) is a chromatin disease caused by loss-of-function variants of the ATRX gene (MIM: *300032) on Xq21.2, encoding ATRX protein, one of the five classes of the ATP-dependent chromatin remodelling proteins, including SWI/SNF, ISWI, CHD, INO80, and ATRX.
The ATRX gene has two functionally important domains, ADD domains and chromatin remodelling domain, where pathogenic variants are identified in more than 90% of ATR-X syndrome.
One third of patients have de novo mutations in the ATRX gene, and two-thirds of patients’ mothers are carriers of mutations in the ATRX gene, who are healthy in general. However, germline mosaicism should be considered for apparent no-carriers.
ATRX protein binds to Guanine-quadruplexes (G4s) to regulate the expression of neighbouring genes and that loss of function of ATRX leads to reduced gene expression of alpha-globin gene HBA, resulting in α-thalassemia in ATR-X syndrome.
ATRX