Co-inheritance of novel ATRX gene mutation and globin (alpha & beta) gene mutations in transfusion dependent beta-thalassemia patients

摘要

alpha-thalassemia x-linked mental retardation syndrome is a rare inherited intellectual disability disorder due to mutations in the ATRX gene. In our previous study of the prevalence of beta-thalassemia mutations in the Eastern Province of Saudi Arabia, we confirmed the widespread coinheritance of alpha-thalassemia mutation. Some of these subjects have a family history of mental retardation, the cause of which is unknown. Therefore, we investigated the presence or absence of mutations in the ATRX gene in these patients. Three exons of the ATRX gene and their flanking regions were directly sequenced. Only four female transfusion dependent beta-thalassemia patients were found to be carriers of a novel mutation in the ATRX gene. Two of the ATRX gene mutations, c.623delA and c.848T>C were present in patients homozygous for IVS I-5(G -> C) and homozygous for Cd39(C -> T) beta-thalassemia mutation, respectively. While the other two that were located in the intronic region (flanking regions), were present in patients homozygous for Cd39(C -> T) beta-thalassemia mutation. The two subjects with the mutations in the coding region had family members with mental retardation, which suggests that the novel frame shift mutation and the missense mutation at coding region of ATRX gene are involved in ATRX syndrome. (C) 2015 Elsevier Inc. All rights reserved.