Human Genetics

, Volume 77, Issue 4, pp 329–334 | Cite as

Hereditary pyropoikilocytosis and elliptocytosis in a Caucasian family

Transmission of the same molecular defect in spectrin through three generations with different clinical expression
  • M. C. Lecomte
  • D. Dhermy
  • M. Garbarz
  • C. Feo
  • H. Gautero
  • O. Bournier
  • C. Picat
  • I. Chaveroche
  • C. Galand
  • P. Boivin
Original Investigations
Received:
Revised:

Summary

Hereditary pyropoikilocytosis (HPP) is a severe hemolytic anemia characterized by a material instability of the red cell membrane leading to cell fragmentation. This fragility may be correlated with functional and structural defects of spectrin. Most HPP patients have been black. We now report three HPP patients from a Caucasian family, the proposita and her two maternal uncles. The proposita's mother and daughter presented mild type I hereditary elliptocytosis (HE), while the proposita's father was clinically and hematologically normal. Our studies revealed a defective ability of spectrin to self-associate, resulting in an excess of spectrin dimer in 4°C extracts in the three HPP patients and to a similar extent in HE relatives. Limited tryptic digestion of spectrin showed a molecular variant in the αI domain as expressed by a decreased amount of 80 000-dalton peptide with a concomitant increase in the 74 000-dalton peptide. Investigations in the proposita's father revealed no abnormalities of the erythrocyte membrane. The co-transmission of HPP and HE phenotypes in the same lineage might suggest variability in the clinical expression of the same molecular defect and lead us to discuss the hypothesis of a double heterozygosity in HPP patients.

Keywords

Anemia Molecular Variant Hemolytic Anemia Erythrocyte Membrane Tryptic Digestion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Agre P, Casella JF, Zinkham WH, McMillan C, Bennett V (1985) Partial deficiency of erythrocyte spectrin in hereditary spherocytosis. Nature 314:380–383Google Scholar
  2. Clarke M (1971) Isolation characterization of a water soluble protein for bovine erythrocyte membrane. Biochem Biophys Res Commun 45:1063–1070Google Scholar
  3. Coetzer TL, Palek J (1986) Partial spectrin deficiency in hereditary pyropoikilocytosis. Blood 67:919–924Google Scholar
  4. Coetzer T, Zail Z (1982) Spectrin tetramer-dimer equilibrium in hereditary elliptocytosis. Blood 59:900–905Google Scholar
  5. Cohen CM (1983) The molecular organization of the red cell membrane skeleton. Semin Hematol 20:141–158Google Scholar
  6. Dhermy D, Féo C, Garbarz M, Bournier O, Dommergues JP, Garcia J, Boivin P, Tchernia J (1983) Anemie hémolytique congénitale par instabilité thermique érythrocytaire et défaut de tétramérisation de la spectrine. Nouv Rev Fr Hematol 25:7–16Google Scholar
  7. Dhermy D, Lecomte MC, Garbarz M, Féo C, Gautero H, Bournier O, Herrera A, Grétillat F, Boivin P (1984a) Molecular defect of spectrin in the family of a child with congenital hemolytic poikilocytic anemia. Pediatr Res 18:1005–1012Google Scholar
  8. Dhermy D, Garbarz M, Girot R, Féo C, Bournier O, Chaveroche I, Boivin P (1984b) A case of clinically recessive hereditary spherocytosis (HS) with spectrin self-association defect in solution and spectrin deficiency in membrane. Blood 64:25a (abstr)Google Scholar
  9. Dhermy D, Garbarz M, Lecomte MC, Féo C, Bournier O, Chaveroche I, Gautero H, Galand C, Boivin P (1986) Hereditary elliptocytosis: clinical morphological biochemical studies of 38 cases. Nouv Rev Fr Hematol 28:129–140Google Scholar
  10. Evans JPM, Baines AJ, Hann IM, Al Hakim I, Knowles SM, Hoffrand AV (1983) Defective spectrin dimer-dimer association in a family with transfusion dependent homozygous hereditary elliptocytosis. Br J Haematol 54:163–172Google Scholar
  11. Féo C, Nossal N, Jones E, Bessis M (1982) Une nouvelle technique d'étude de la physiologie des globules rouges: la mesure de leur déformabilité en fonction de l'osmolarité. Résultats obtenus par un ektacytomètre automatisé sur le sang normal et dans différentes anémies hémolytiques. CR Acad Sci [Ser D] 295:687–691Google Scholar
  12. Garbarz M, Lecomte MC, Dhermy D, Féo C, Chaveroche I, Gautero H, Bournier O, Picat, C, Goepp A, Boivin P (1986) Double inheritance of an 334-1 spectrin variant in a child with hoomozygous elliptocytosis. Blood 67:1661–1667Google Scholar
  13. Groner W, Mohandas N, Bessis M (1980) New optical technique for measuring erythrocyte deformability with the ektacytometer. Clin Chem 26:1435–1442Google Scholar
  14. Knowles WJ, Morrow JS, Speicher DW, Zarkowsky HS, Mohandas N, Mentzer WC, Shohet SB (1983) Molecular functional changes in spectrin from patients with hereditary pyropoikilocytosis. J Clin Invest 71:1867–1877Google Scholar
  15. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of the bacteriophage T4. Nature 227:680–685Google Scholar
  16. Lawler J, Liu SC, Palek J, Prchal J (1982) Molecular defect of spectrin in hereditary pyropoikilocytosis. Alterations in the trypsin-resistant domain involved in spectrin self-association. J Clin Invest 70:1019–1030Google Scholar
  17. Lawler J, Palek J, Liu SC, Prchal J, Butler WM (1983) Molecular heterogeneity of hereditary pyropoikilocytosis. Identification of a second variant of the spectrin alpha subunit. Blood 62:1182–1189Google Scholar
  18. Lawler J, Liu SC, Palek J, Prchal J (1984) A molecular defect of spectrin in a subset of patients with hereditary elliptocytosis. J Clin Invest 73:1688–1695Google Scholar
  19. Lawler J, Coetzer TL, Palek J, Jacob HS, Luban N (1985) 334-2: a new variant of the α subunit of spectrin in hereditary elliptocytosis. Blood 66:706–709Google Scholar
  20. Lecomte MC, Dhermy D, Garbarz M, Gautero H, Bournier O, Galand C, Boivin P (1984) Hereditary elliptocytosis with a spectrin molecular defect in a white patient. Acta Haematol 71:235–240Google Scholar
  21. Lecomte MC, Dhermy D, Garbarz M, Féo C, Gautero H, Bournier O, Picat C, Chaveroche I, Ester A, Galand C, Boivin P (1985a) Pathologic and non pathologic variants of the spectrin molecule in two black families with hereditary elliptocytosis. Hum Genet 71:351–357Google Scholar
  22. Lecomte MC, Dhermy D, Solis C, Ester E, Féo C, Gautero H, Bournier O, Boivin P (1985b) A new abnormal variant of spectrin in black patients with hereditary elliptocytosis. Blood 65:1208–1217Google Scholar
  23. Liu SC, Palek J, Prchal J, Castleberry RP (1981) Altered spectrin dimer-dimer association, instability of the erythrocyte membrane skeletons in hereditary pyropoikilocytosis. J Clin Invest 68:597–605Google Scholar
  24. Liu SC, Palek J, Prchal J (1982) Defective spectrin dimer-dimer association in hereditary elliptocytosis. Proc Natl Acad Sci USA 79:2072–2076Google Scholar
  25. Marchesi SL, Knowles WJ, Morrow JS, Bologna M, Marchesi VT (1986) Abnormal spectrin in hereditary elliptocytosis. Blood 67:141–151Google Scholar
  26. Mentzer WC, Turetsky T, Mohandas N, Schrier S, Wu CS, Koenig H (1984a) Identification of the hereditary pyropoikilocytosis carrier state. Blood 63:1439–1446Google Scholar
  27. Mentzer WC, Iarooci TA, Mohandas N (1984b) Modulation of RBC membrane mechanical fragility by 2-3-DPG in transient neonatal poikilocytosis. Blood 64:28a (abstr)Google Scholar
  28. Mohandas N, Clark CM, Heath BP, Rossi M, Wolfe L, Lux S, Shohet SB (1982) Technics to detect reduced mechanical stability of red cell membrane. Relevance to elliptocytosis disorder. Blood 59:768–774Google Scholar
  29. Morris SA, Ohanian V, Lewis MC, Chahwala SB, Rodeck CH, Mibrashan RS, Gratzer WB (1986) Prenatal diagnosis of hereditary red cell membrane defect. Br J Haematol 52:763–772Google Scholar
  30. O'Farrell P (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250:4007–4021Google Scholar
  31. Palek J, Lux SE (1983) Red cell membrane skeletal defects in hereditary acquired hemolytic anemias. Semin Hematol 20:189–224Google Scholar
  32. Sheetz MP, Casaly J (1980) 2-3-Diphosphoglycerate and ATP dissociate erythrocyte membrane skeletons. J Biol Chem 255:9955–9960Google Scholar
  33. Speicher DW, Morrow JS, Knowles WJ, Marchesi VT (1982) A structural model of human erythrocyte spectrin alignment of chemical functional domains. J Biol Chem 257:9093–9101Google Scholar
  34. Zarkowsky HS, Mohandas N, Speaker CB, Shohet SB (1975) A congenital haemolytic anaemia with thermal sensibility of the erythrocyte membrane. Br J Haematol 29:537–543Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • M. C. Lecomte
    • 1
  • D. Dhermy
    • 2
  • M. Garbarz
    • 2
  • C. Feo
    • 2
  • H. Gautero
    • 2
  • O. Bournier
    • 2
  • C. Picat
    • 2
  • I. Chaveroche
    • 2
  • C. Galand
    • 2
  • P. Boivin
    • 2
  1. 1.Unité de Recherches d'Enzymologie des Cellules Sanguines (INSERM U160)Hôpital BeaujonClichy CedexFrance
  2. 2.Institut de Pathologie Cellulaire (INSERM U 299)Hôpital BicêtreKremlin-BicêtreFrance

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