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Molecular determinants of clinical expression of hereditary elliptocytosis and pyropoikilocytosis.
Blood. 1987 Sep; 70(3):766-72.Blood

Abstract

The clinical severity of common hereditary elliptocytosis (HE) is highly variable, ranging from an asymptomatic carrier state to a severe hemolytic anemia. To elucidate the molecular basis of this variable clinical expression, we evaluated 56 subjects from 24 HE kindred, who carry alpha spectrin mutants characterized by a spectrin dimer (SpD) self-association defect related to a structural abnormality of the alpha I domain of spectrin. Twenty-nine subjects had common HE, 13 subjects have a closely related disorder, hereditary pyropoikilocytosis (HPP), and 14 are asymptomatic carriers. We compared the severity of hemolysis with the following biochemical parameters: (a) spectrin heterodimer self-association, as manifested by the percentage of SpD in the 4 degrees C low ionic strength spectrin extract; (b) spectrin structure, as examined by limited tryptic digestion of spectrin; and (c) spectrin content of the RBC membrane. Our analysis indicates that the severity of hemolysis may be correlated with quantitative differences in the percentage of SpD in the 4 degrees C spectrin extract, as well as the total spectrin content of the membrane. Thus, HPP subjects, who have the most severe hemolytic anemia, have the highest percentage of SpD as well as a decreased spectrin content. HE subjects and asymptomatic carriers, respectively, have a lower percentage of SpD and a normal spectrin content. Factors influencing these two determinants include functional differences between the individual spectrin mutants, the relative amounts of mutant spectrin present in the cells, the stability of mutant spectrin, and the possibility of a superimposed genetic defect involving spectrin synthesis.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

3620700

Citation

Coetzer, T, et al. "Molecular Determinants of Clinical Expression of Hereditary Elliptocytosis and Pyropoikilocytosis." Blood, vol. 70, no. 3, 1987, pp. 766-72.
Coetzer T, Lawler J, Prchal JT, et al. Molecular determinants of clinical expression of hereditary elliptocytosis and pyropoikilocytosis. Blood. 1987;70(3):766-72.
Coetzer, T., Lawler, J., Prchal, J. T., & Palek, J. (1987). Molecular determinants of clinical expression of hereditary elliptocytosis and pyropoikilocytosis. Blood, 70(3), 766-72.
Coetzer T, et al. Molecular Determinants of Clinical Expression of Hereditary Elliptocytosis and Pyropoikilocytosis. Blood. 1987;70(3):766-72. PubMed PMID: 3620700.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular determinants of clinical expression of hereditary elliptocytosis and pyropoikilocytosis. AU - Coetzer,T, AU - Lawler,J, AU - Prchal,J T, AU - Palek,J, PY - 1987/9/1/pubmed PY - 1987/9/1/medline PY - 1987/9/1/entrez SP - 766 EP - 72 JF - Blood JO - Blood VL - 70 IS - 3 N2 - The clinical severity of common hereditary elliptocytosis (HE) is highly variable, ranging from an asymptomatic carrier state to a severe hemolytic anemia. To elucidate the molecular basis of this variable clinical expression, we evaluated 56 subjects from 24 HE kindred, who carry alpha spectrin mutants characterized by a spectrin dimer (SpD) self-association defect related to a structural abnormality of the alpha I domain of spectrin. Twenty-nine subjects had common HE, 13 subjects have a closely related disorder, hereditary pyropoikilocytosis (HPP), and 14 are asymptomatic carriers. We compared the severity of hemolysis with the following biochemical parameters: (a) spectrin heterodimer self-association, as manifested by the percentage of SpD in the 4 degrees C low ionic strength spectrin extract; (b) spectrin structure, as examined by limited tryptic digestion of spectrin; and (c) spectrin content of the RBC membrane. Our analysis indicates that the severity of hemolysis may be correlated with quantitative differences in the percentage of SpD in the 4 degrees C spectrin extract, as well as the total spectrin content of the membrane. Thus, HPP subjects, who have the most severe hemolytic anemia, have the highest percentage of SpD as well as a decreased spectrin content. HE subjects and asymptomatic carriers, respectively, have a lower percentage of SpD and a normal spectrin content. Factors influencing these two determinants include functional differences between the individual spectrin mutants, the relative amounts of mutant spectrin present in the cells, the stability of mutant spectrin, and the possibility of a superimposed genetic defect involving spectrin synthesis. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/3620700/Molecular_determinants_of_clinical_expression_of_hereditary_elliptocytosis_and_pyropoikilocytosis_ L2 - http://www.diseaseinfosearch.org/result/3352 DB - PRIME DP - Unbound Medicine ER -