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

Blood Cells Mol Dis. 2015 Jun;55(1):27-9. doi: 10.1016/j.bcmd.2015.03.008. Epub 2015 Mar 30.

Abstract

α-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 β-thalassemia mutations in the Eastern Province of Saudi Arabia, we confirmed the widespread coinheritance of α-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 β-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) β-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) β-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.

Keywords: ATRX gene; Mental retardation; α-thalassemia; β-thalassemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Blood Transfusion
  • DNA Helicases / genetics*
  • Exons
  • Female
  • Heterozygote
  • Homozygote
  • Humans
  • Introns
  • Male
  • Mental Retardation, X-Linked / complications
  • Mental Retardation, X-Linked / genetics*
  • Mental Retardation, X-Linked / pathology
  • Mental Retardation, X-Linked / therapy
  • Molecular Sequence Data
  • Mutation*
  • Nuclear Proteins / genetics*
  • Pedigree
  • Saudi Arabia
  • X-linked Nuclear Protein
  • alpha-Globins / genetics*
  • alpha-Thalassemia / complications
  • alpha-Thalassemia / genetics*
  • alpha-Thalassemia / pathology
  • alpha-Thalassemia / therapy
  • beta-Globins / genetics*
  • beta-Thalassemia / complications
  • beta-Thalassemia / genetics*
  • beta-Thalassemia / pathology
  • beta-Thalassemia / therapy

Substances

  • Nuclear Proteins
  • alpha-Globins
  • beta-Globins
  • DNA Helicases
  • ATRX protein, human
  • X-linked Nuclear Protein

Supplementary concepts

  • ATR-X syndrome