The c.2101A>G synonymous change (p.G674G) in the gene for ATR, a key player in the DNA-damage response, has been the first identified genetic cause of Seckel Syndrome (SS), an orphan disease characterized by growth and mental retardation.
Two of the syndromes, ATR-16 and ATR-X, are characterized by α-thalassemia in association with multiple developmental abnormalities including mental retardation.
The much less common disorders, ATR-16 and ATR-X are also providing valuable information about the spectrum of molecular lesions associated with different forms of mental retardation and about the molecular mechanisms involved in their varying phenotypes.
The region on chromosome 16p for which haploinsufficiency leads to the dysmorphic features and MR typical for ATR-16, has been narrowed down to a 800 kb region localized between 0.9 and 1.7 Mb from the telomere.
We now report on a second instance of a patient presenting with mental retardation and asplenia who has been shown to have a mutation at the ATR-X locus.
Mutations in the XNP gene have been reported in alpha thalassemia/mental retardation (MR) syndrome (ATR-X) and other severe X-linked MR conditions with facial dysmorphisms.
We used monoclonal antibodies directed against the XNP/ATR-X protein and performed immunocytochemical and western blot analyses, which showed altered or absent XNP/ATR-X expression in cells of affected patients.