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A Podda, R Galanello, L Maccioni, MA Melis, C Rosatelli, L Perseu and A Cao
Istituto di Clinica e Biologia Eta Evolutiva, Universita Studi Cagliari,
Italy.
This report describes a patient with thalassemia intermedia-like phenotype
born to normal parents in whom globin gene sequencing detected a novel
abnormal hemoglobin (Hb) due to a T to A substitution at codon 60 of the
beta-globin gene arising as a de novo mutation. Normal sequences were
detected at the homologous beta-globin locus. This mutation results in the
substitution of a polar (glutamic acid) for a nonpolar (valine) residue
near the corner of the heme pocket of the beta-globin chain. The novel
variant has been designated Hb Cagliari, from the place of birth of the
propositus. Kinetics of globin synthesis performed following splenectomy
suggest that this new Hb variant is synthesized at a near normal rate but
undergoes rapid breakdown. The extreme lability of the variant explains the
clinical and hematologic picture characterized by marked ineffective
erythropoiesis, thalassemia-like bone changes, iron overload, high
proportion of Hb F in the peripheral blood, reduced beta/alpha-globin chain
synthesis ratio in peripheral blood reticulocytes, and absence of the
abnormal Hb in peripheral blood at extensive protein structural analysis
before splenectomy. This case indicates that a thalassemic hemoglobinopathy
should be suspected in the presence of a patient with a thalassemia
intermedia-like phenotype born to normal parents, even when protein
structural analysis fails to detect an abnormal Hb. DNA sequencing may
allow to define the mutation, thus making the proper diagnosis.
This article has been cited by other articles:
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| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
