Al-Nafie Awatif N, Borgio J Francis, AbdulAzeez Sayed, Al-Suliman Ahmed M, Qaw Fuad S, Naserullah Zaki A, Al-Jarrash Sana, Al-Madan Mohammed S, Al-Ali Rudaynah A, AlKhalifah Mohammed A, Al-Muhanna Fahad, Steinberg Martin H, Al-Ali Amein K
Department of Pathology, University of Dammam, Dammam, Saudi Arabia.
Centre for Medical Research and Consultation, University of Dammam, Dammam, Saudi Arabia.
Blood Cells Mol Dis. 2015 Jun;55(1):27-9. doi: 10.1016/j.bcmd.2015.03.008. Epub 2015 Mar 30.
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.
α地中海贫血X连锁智力发育迟缓综合征是一种罕见的遗传性智力残疾疾病，由ATRX基因突变引起。在我们之前对沙特阿拉伯东部省份β地中海贫血突变患病率的研究中，我们证实了α地中海贫血突变的广泛共遗传现象。这些受试者中的一些人有智力发育迟缓的家族史，但其病因不明。因此，我们调查了这些患者中ATRX基因是否存在突变。对ATRX基因的三个外显子及其侧翼区域进行了直接测序。仅发现四名依赖输血的女性β地中海贫血患者是ATRX基因新突变的携带者。其中两个ATRX基因突变，即c.623delA和c.848T>C，分别存在于IVS I-5(G→C)纯合子和Cd39(C→T)β地中海贫血突变纯合子患者中。而另外两个位于内含子区域（侧翼区域）的突变，则存在于Cd39(C→T)β地中海贫血突变纯合子患者中。两名编码区有突变的受试者有智力发育迟缓的家庭成员，这表明ATRX基因编码区的新型移码突变和错义突变与ATRX综合征有关。
