title: Co-inheritance of novel ATRX gene mutation and globin (α & β) gene mutations in transfusion dependent beta-thalassemia patients.
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.
authors.affiliation: Department of Pathology, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Awatif N
authors.initials: AN
authors.lastname: Al-Nafie
authors.affiliation: Centre for Medical Research and Consultation, University of Dammam, Dammam, Saudi Arabia. Electronic address: borgiomicro@gmail.com.
authors.forename: J Francis
authors.initials: JF
authors.lastname: Borgio
authors.affiliation: Centre for Medical Research and Consultation, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Sayed
authors.initials: S
authors.lastname: AbdulAzeez
authors.affiliation: Al-Omran Scientific Chair for Hematological Diseases in Al-Ahsa, King Faisal University, Al-Ahsa, Saudi Arabia; Department of Hematology, King Fahd Hospital, Al-Ahsa, Saudi Arabia.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Al-Suliman
authors.affiliation: Department of Biochemistry, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Fuad S
authors.initials: FS
authors.lastname: Qaw
authors.affiliation: Dammam Maternity and Child Hospital, Dammam, Saudi Arabia.
authors.forename: Zaki A
authors.initials: ZA
authors.lastname: Naserullah
authors.affiliation: Dammam Maternity and Child Hospital, Dammam, Saudi Arabia.
authors.forename: Sana
authors.initials: S
authors.lastname: Al-Jarrash
authors.affiliation: Department of Pediatrics, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Al-Madan
authors.affiliation: Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia.
authors.forename: Rudaynah A
authors.initials: RA
authors.lastname: Al-Ali
authors.affiliation: Qatif Central Hospital, Qatif, Saudi Arabia.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: AlKhalifah
authors.affiliation: Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia.
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Muhanna
authors.affiliation: Center of Excellence in Sickle Cell Disease, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
authors.affiliation: Centre for Medical Research and Consultation, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Amein K
authors.initials: AK
authors.lastname: Al-Ali
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001803:Blood Transfusion; D004265:DNA Helicases / Q000235:genetics*; D005091:Exons; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D008297:Male; D038901:X-Linked Intellectual Disability / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D012529:Saudi Arabia; D000075924:X-linked Nuclear Protein; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000628:therapy
chemical_list: D009687:Nuclear Proteins; D055542:alpha-Globins; D055544:beta-Globins; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
keywords: ATRX gene; Mental retardation; α-thalassemia; β-thalassemia