Disease relevance of alpha-Thalassemia

• Exceptions in which deletions do account for the majority of observed abnormalities include the alpha-thalassemias, Duchenne muscular dystrophy, and steroid sulfatase deficiency [1].
• We have examined a large Asian Indian pedigree which includes individuals with heterocellular HPFH associated with beta-thalassemia and/or alpha-thalassemia [2].
• The deletions in the zeta-alpha globin gene cluster in two infants with the hemoglobin Bart's hydrops fetalis syndrome (homozygous alpha thalassemia 1) have been mapped by restriction endonuclease analysis using a zeta-specific probe [3].
• Hemoglobin (Hb) Constant Spring is an alpha-thalassemic hemoglobinopathy that is a major cause of severe alpha-thalassemia in Southeast Asians [4].
• As a follow-up to this report, we studied the antimalarial kinetics of intravascular artesunate (2.4 mg/kg of body weight) in 10 persons with normal hemoglobins and in 10 patients with thalassemia (2 with alpha-thalassemia type 1-hemoglobin Constant Spring and 8 with alpha-thalassemia type 1-alpha-thalassemia type 2) [5].

Psychiatry related information on alpha-Thalassemia

• Daxx accumulates in both the nucleus and the cytoplasm; in the nucleus, Daxx is found associated with the promyelocytic leukaemia (PML) nuclear body and with alpha-thalassemia/mental retardation syndrome protein (ATRX)-positive heterochromatic regions [6].
• Single gene conditions include methylene tetrahydrofolate reductase deficiency (MTHFR), Rett syndrome, alpha-thalassemia retardation syndrome (ATR-X), and Gurrieri syndrome [7].

High impact information on alpha-Thalassemia

• We recently described an individual with an inherited form of anemia (alpha-thalassemia) who has a deletion that results in a truncated, widely expressed gene (LUC7L) becoming juxtaposed to a structurally normal alpha-globin gene (HBA2) [8].
• B12 deficiency in alpha-thalassemia [9].
• In both deletion and nondeletion forms of alpha thalassemia, only the alpha 1 RNA and establish the normal pattern of relative alpha-gene expression during development independent of protein variants [10].
• The results show that there are two common alpha-thalassemia haplotypes, a deletion (-alpha/) determinant and a nondeletion (alpha alpha T/) determinant, which interact to produce a series of overlapping phenotypes [11].
• In a Chinese patient with nondeletion hemoglobin-H disease (- -/alpha alpha T) (both alpha-globin genes are present but not fully functional) a normal ratio was maintained between the levels of alpha 1- and alpha 2-globin mRNA, implying that mRNA production from both alpha-globin genes is suppressed in a balanced manner [12].

Chemical compound and disease context of alpha-Thalassemia

• Molecular basis for nondeletion alpha-thalassemia in American blacks. Alpha 2(116GAG----UAG) [13].
• In the other patient, Hb Camden (beta-131 gln leads to glu) was identified, and the hematologic findings also indicated that he has alpha-thalassemia trait [14].
• Methylhydrazine, in contrast, induced selective association of oxidized beta-globin chains with the membrane skeleton and produced rigid but hyperstable membranes, features that mimicked those of RBCs in severe alpha-thalassemia [15].
• Poor tolerance of zidovudine in an HIV-asymptomatic patient with alpha-thalassemia [16].
• Individuals with alpha thalassemia trait and normal iron studies had FEP levels in the normal range despite marked degrees of microcytosis [17].

Biological context of alpha-Thalassemia

• Biosynthetic studies of blood from 15 subjects revealed balanced synthesis of alpha and beta globin chains in heterozygotes from all three classes, strongly supporting variable gene dosage rather than alpha-thalassemia as the mechanism underlying the observed trimodality in the proportion of Hb G [18].
• Analysis of copy number variants of the duplicated alpha-, zeta-, and gamma-globin genes in eastern Polynesians revealed a high frequency of both triplicated-zeta-gene chromosomes and a specific alpha thalassemia deletion [19].
• Gene deletions in alpha thalassemia prove that the 5' zeta locus is functional [3].
• X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis [20].
• The coinheritance of a nondeletional form of alpha thalassemia (alpha alpha T) was suspected because of the severity of the proband's phenotype and the presence of normal alpha-globin gene fragments in the father [21].

Anatomical context of alpha-Thalassemia

• Erythrocytes associated with minor or no clinical symptoms (eg, alpha-thalassemia traits, hemoglobin [Hb] E trait, Hb Constant Spring trait), which showed only a minimal decrease in deformability, were, in general, invaded efficiently by the malarial parasite Plasmodium falciparum [22].
• We have disrupted the 5' locus of the duplicated adult alpha-globin genes by gene targeting in the mouse embryonic stem cells and created mice with alpha-thalassemia syndromes [23].
• Prevalence of hemoglobin E, alpha-thalassemia and glucose-6-phosphate dehydrogenase deficiency in 1,000 cord bloods studied in Bangkok [24].

Gene context of alpha-Thalassemia

• Common clinical features associated with ATRX mutations include severe mental retardation, characteristic facial anomalies and variable degrees of urogenital defects and alpha-thalassemia [25].
• The alpha-globin chains are encoded by two duplicated genes (HBA2 and HBA1, 5'-3') showing overall sequence homology >96% and average CG content >60%. alpha-Thalassemia, the most prevalent worldwide autosomal recessive disorder, is a hereditary anemia caused by sequence variations of these genes in about 25% of carriers [26].
• This RBC CR1 deficiency is associated with polymorphisms in the CR1 gene and, unexpectedly, with alpha-thalassemia, a common genetic disorder in Melanesian populations [27].
• Mouse zeta- and alpha-globin genes: embryonic survival, alpha-thalassemia, and genetic background effects [28].
• The distribution of alpha-thalassemia 2 seems to be in accordance with other conditions such as ovalocytosis and G6PD deficiency which are also prevalent in this population, suggesting that they may interact in protection against malaria [29].

Analytical, diagnostic and therapeutic context of alpha-Thalassemia

• Restriction enzyme mapping established the origin of the alpha-thalassemia gene as the more 3' of the normal, duplicated alpha genes (alpha 1) [30].
• Analysis of a case-control study demonstrated that the CR1 polymorphisms and alpha-thalassemia independently confer protection against severe malaria [27].
• Homozygous alpha-thalassemia treated with intrauterine transfusions and postnatal hematopoietic stem cell transplantation [31].
• Gene mapping of Malaysian alpha thalassemias with alpha and zeta globin gene probes [32].
• We evaluated potential screening protocols for alpha-thalassemia in a group of 80 patients whose genotypes were determined by Southern blot analysis with alpha- and zeta-globin DNA probes [33].

References