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Hemoglobin Petah Tikva (alpha 110 ala replaced by asp): a new unstable variant with alpha-thalassemia-like expression

1981; Elsevier BV; Volume: 57; Issue: 4 Linguagem: Inglês

10.1182/blood.v57.4.705.705

1528-0020

GR Honig, Mir Shamsuddin, Rina Zaizov, M Steinherz, I Solar, C Kirschmann,

Iron Metabolism and Disorders

Abstract Hemoglobin Petah Tikva, a new unstable α-Chain structural variant, was identified in two unrelated children whose families are from the Iraqi Jewish community of Baghdad. Both children have α-thalassemia. with hematologic features of mild HbH disease. The abnormal hemoglobin from the two patients did not separate from hemoglobin A by electrophoresis or chromatography, but the mutant α-chain emerged ahead of αA in carboxymethylcellulose column chromatography, allowing it to be isolated in pure form. Hemoglobin Petah Tikva was unstable in solution and could also be isolated by isopropanol precipitation. Structural analyses indicate that the variant α-Chains contain a normal number of amino acids and have a substitution of Ala → Asp at α 110. Each of the patients with HbH disease has one parent with hematologic findings and globin chain synthesis ratios that are characteristic of α-thalassemia trait, and a hematologically normal parent who is a carrier of the variant α-chain of Hb Petah Tikva. The patients each appear to be doubly heterozygous for α-thal-1 and for the structurally abnormal hemoglobin. The mutant α-chains of Hb Petah Tikva were synthesized by reticulocytes of the heterozygous carriers, but only traces of αPT globin could be detected in their blood, suggesting that the abnormal α-chains underwent postsynthetic degradation or precipitation in these individuals. In the patients with Hb Petah Tikva in combination with α-thalassemia, the normal and mutant α-chains were synthesized by bone marrow erythroid cells at rates proportional to their concentrations in the blood, but there was a substantially decreased rate of synthesis of the variant α-chain by their blood reticulocytes. The α-thalassemia-like expression of Hb Petah Tikva appears to result from instability of the abnormal α-chain as well as from the premature termination of its synthesis during erythroid cell maturation.