Abstract
Studies of erythrocyte spectrin were performed in a patient with hemolytic anemia and her family to understand the biochemical and genetic basis of HPP. The proband had decreased stability of her red cells when exposed to 45°C, typical of HPP. Her cytoskeleton exhibited instability to shear stress. There was an increase in the amount of spectrin dimers in a crude 4°C spectrin extract (58% compared to control value of 6±4%) indicating a decrease in spectrin dimer-dimer association. A structural analysis of her spectrinα I domain by limited tryptic digestion revealed a decrease in the normal 80000 dalton fragment and an increase in fragments of 74000, 61000, 55000, 21000 and 16000 daltons. A 25% decrease, relative to control in the spectrin to band 3 ratio on SDS-PAGE demonstrated partial spectrin deficiency in the membrane. On a discontinuous Percoll-Renograf in gradient, the patient exhibited the presence of cells at higher densities than that found with control cells. Both parents are asymptomatic carriers with increased amounts of spectrin dimers at levels that are intermediate between the control and the patient. The father's digest had increased amounts of the 74000 dalton peptide, while the mother's digest had increased amounts of the 61000, 55000, 21000 and 16000 dalton fragments. The biochemical and genetic basis of this severe HPP is probably a double heterozygous state, one of which is a previously undescribed molecular defect of spectrin.
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Lawler, J., Coetzer, T., Mankad, V. et al. IDENTIFICATION OF A NEW STRUCTURAL VARIANT OF α SPECTRIN IN A DOUBLE HETEROZYGOUS FORM OF HEREDITARY PYROPOIKILOCYTOSIS (HPP). Pediatr Res 21 (Suppl 4), 301 (1987). https://doi.org/10.1203/00006450-198704010-00802
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DOI: https://doi.org/10.1203/00006450-198704010-00802