Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Variant hemoglobins such as Hb Lepore and Hb Constant Spring, because of their low synthetic rates, produce the phenotypes of beta and alpha-thalassemia respectively. A new hemoglobin variant, Hb Indianapolis, produced the phenotype of severe beta-thalassemia due to its extreme lability. Hb Indianapolis was so unstable that it no detectable protein associated with it could be isolated from the hemolysates of affected individuals. Structural analysis, using only radioactivity, revealed a cysteine to arginine substitution at beta 112 (G14). The extremely rapid precipitation and catabolism of beta Indianapolis and the resulting excess of alpha-chains, both causing membrane damage, may be responsible for the severe clinical manifestations associated with this variant. Another new hemoglobin variant, Hb Vicksburg, was found to produce the phenotype of thalassemia intermedia in the proband who was doubly heterozygous for this variant and beta 0-thalassemia. Structural analysis of Hb Vicksburg demonstrated a deletion of leucine at beta 75 (E19). Hb Vicksburg should have comprised the major portion of the hemolysate in the proband because of the presence of beta 0-thalassemia on the trans chromosome, but comprised instead only 7.6%. Thus, Hb Vicksburg was synthesized at a rate lower than that expected on the basis of gene dosage. Deletion of beta 75, for a number of reasons, would not be expected to lead to diminished synthesis of the variant. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for beta +-thalassemia is present in cis to the structural mutation. Hb Indianapolis and Hb Vicksburg, therefore, are two new hemoglobin variants which produce the phenotype of beta-thalassemia by widely different mechanisms.
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PMID:Low output hemoglobins which produce the phenotype of thalassemia. 689 57