Seminars in Hematology
Volume 41, Issue 2 , Pages 142-164 , April 2004

Hereditary elliptocytosis: spectrin and protein 4.1R

  • Patrick G Gallagher

      Affiliations

    • Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA
    • Corresponding Author InformationAddress correspondence to Patrick G. Gallagher, MD, Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, PO Box 208064, New Haven, CT 06520-8064 USA

References 

  1. Lecomte MC, Dhermy D, Gautero H, et al.  Hereditary elliptocytosis in West Africa (frequency and repartition of spectrin variants (in French)). C R Acad Sci. 1988;306:43–46
  2. Ganesan J, George R, Lie-Injo LE. Abnormal haemoglobins and hereditary ovalocytosis in the Ulu Jempul District of Kuala Pilah, West Malaysia. Southeast Asian J Trop Med Public Health. 1976;7:430–433
  3. Glele-Kakai C, Garbarz M, Lecomte MC, et al.  Epidemiological studies of spectrin mutations related to hereditary elliptocytosis and spectrin polymorphisms in Benin. Br J Haematol. 1996;95:57–66
  4. McCarty SH. Elliptical red blood cells in man. A report of eleven cases. J Lab Clin Med. 1934;19:612
  5. Wyandt H, Bancroft PM, Winship TO. Elliptic erythrocytes in man. Arch Intern Med. 1941;68:1043–1065
  6. Hunter WC. Further study of a white family showing elliptical erythrocytes. Ann Intern Med. 1932;6:775–781
  7. Hunter WC, Adams RB. Hematologic study of three generations of a white family showing elliptical erythrocytes. Ann Intern Med. 1929;2:1162–1174
  8. Lecomte MC, Garbarz M, Gautero H, et al.  Molecular basis of clinical and morphological heterogeneity in hereditary elliptocytosis (HE) with spectrin alpha I variants. Br J Haematol. 1993;85:584–595
  9. Lorenzo F, Miraglia del Giudice E, Alloisio N, et al.  Severe poikilocytosis associated with a de novo alpha 28 Arg→Cys mutation in spectrin. Br J Haematol. 1993;83:152–157
  10. McGuire M, Smith BL, Agre P. Distinct variants of erythrocyte protein 4.1 inherited in linkage with elliptocytosis and Rh type in three white families. Blood. 1988;72:287–293
  11. Palek J, Lambert S. Genetics of the red cell membrane skeleton. Semin Hematol. 1990;27:290–332
  12. Coetzer T, Lawler J, Prchal JT, et al.  Molecular determinants of clinical expression of hereditary elliptocytosis and pyropoikilocytosis. Blood. 1987;70:766–772
  13. Coetzer T, Palek J, Lawler J, et al.  Structural and functional heterogeneity of alpha spectrin mutations involving the spectrin heterodimer self-association site (Relationships to hematologic expression of homozygous hereditary elliptocytosis and hereditary pyropoikilocytosis). Blood. 1990;75:2235–2244
  14. Coetzer TL, Sahr K, Prchal J, et al.  Four different mutations in codon 28 of alpha spectrin are associated with structurally and functionally abnormal spectrin alpha I/74 in hereditary elliptocytosis. J Clin Invest. 1991;88:743–749
  15. Discher D, Parra M, Conboy JG, et al.  Mechanochemistry of the alternatively spliced spectrin-actin binding domain in membrane skeletal protein 4.1. J Biol Chem. 1993;268:7186–7195
  16. Jonsson JJ, Renieri A, Gallagher PG, et al.  Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis (A new X linked contiguous gene deletion syndrome?). J Med Genet. 1998;35:273–278
  17. Tse WT, Lux SE. Red blood cell membrane disorders. Br J Haematol. 1999;104:2–13
  18. Gallagher PG, Ferriera JD. Molecular basis of erythrocyte membrane disorders. Curr Opin Hematol. 1997;4:128–135
  19. del Giudice EM, Ducluzeau MT, Alloisio N, et al.  Alpha I/65 hereditary elliptocytosis in southern Italy (Evidence for an African origin). Hum Genet. 1992;89:553–556
  20. Gallagher PG, Tse WT, Coetzer T, et al.  A common type of the spectrin alpha I 46–50a-kD peptide abnormality in hereditary elliptocytosis and pyropoikilocytosis is associated with a mutation distant from the proteolytic cleavage site. Evidence for the functional importance of the triple helical model of spectrin. J Clin Invest. 1992;89:892–898
  21. Sahr KE, Laurila P, Kotula L, et al.  The complete cDNA and polypeptide sequences of human erythroid alpha-spectrin. J Biol Chem. 1990;265:4434–4443
  22. Winkelmann JC, Chang JG, Tse WT, et al.  Full-length sequence of the cDNA for human erythroid beta-spectrin. J Biol Chem. 1990;265:11827–11832
  23. Winkelmann JC, Forget BG. Erythroid and nonerythroid spectrins. Blood. 1993;81:3173–3185
  24. Harper SL, Begg GE, Speicher DW. Role of terminal nonhomologous domains in initiation of human red cell spectrin dimerization. Biochemistry. 2001;40:9935–9943
  25. Lenne PF, Raae AJ, Altmann SM, et al.  States and transitions during forced unfolding of a single spectrin repeat. FEBS Lett. 2000;476:124–128
  26. Pascual J, Pfuhl M, Walther D, et al.  Solution structure of the spectrin repeat (A left-handed antiparallel triple-helical coiled-coil). J Mol Biol. 1997;273:740–751
  27. Rief M, Pascual J, Saraste M, et al.  Single molecule force spectroscopy of spectrin repeats (Low unfolding forces in helix bundles). J Mol Biol. 1999;286:553–561
  28. Speicher DW, Marchesi VT. Erythrocyte spectrin is comprised of many homologous triple helical segments. Nature. 1984;311:177–180
  29. Speicher DW, Weglarz L, DeSilva TM. Properties of human red cell spectrin heterodimer (side-to-side) assembly and identification of an essential nucleation site. J Biol Chem. 1992;267:14775–14782
  30. Ursitti JA, Kotula L, DeSilva TM, et al.  Mapping the human erythrocyte beta-spectrin dimer initiation site using recombinant peptides and correlation of its phasing with the alpha-actinin dimer site. J Biol Chem. 1996;271:6636–6644
  31. Winograd E, Hume D, Branton D. Phasing the conformational unit of spectrin. Proc Natl Acad Sci USA. 1991;88:10788–10791
  32. Viel A, Branton D. Interchain binding at the tail end of the Drosophila spectrin molecule. Proc Natl Acad Sci USA. 1994;91:10839–10843
  33. An X, Lecomte MC, Chasis JA, et al.  Shear-response of the spectrin dimer-tetramer equilibrium in the red blood cell membrane. J Biol Chem. 2002;277:31796–31800
  34. Cherry L, Menhart N, Fung LW. Interactions of the alpha-spectrin N-terminal region with beta-spectrin. Implications for the spectrin tetramerization reaction. J Biol Chem. 1999;274:2077–2084
  35. DeSilva TM, Peng KC, Speicher KD, et al.  Analysis of human red cell spectrin tetramer (head-to-head) assembly using complementary univalent peptides. Biochemistry. 1992;31:10872–10878
  36. Kotula L, DeSilva TM, Speicher DW, et al.  Functional characterization of recombinant human red cell alpha-spectrin polypeptides containing the tetramer binding site. J Biol Chem. 1993;268:14788–14793
  37. Lecomte MC, Nicolas G, Dhermy D, et al.  Properties of normal and mutant polypeptide fragments from the dimer self-association sites of human red cell spectrin. Eur Biophys J. 1999;28:208–215
  38. Liu SC, Palek J. Spectrin tetramer-dimer equilibrium and the stability of erythrocyte membrane skeletons. Nature. 1980;285:586–588
  39. Morris SA, Eber SW, Gratzer WB. Structural basis for the high activation energy of spectrin self-association. FEBS Lett. 1989;244:68–70
  40. Park S, Mehboob S, Luo BH, et al.  Studies of the erythrocyte spectrin tetramerization region. Cell Mol Biol Lett. 2001;6:571–585
  41. Speicher DW, DeSilva TM, Speicher KD, et al.  Location of the human red cell spectrin tetramer binding site and detection of a related “closed” hairpin loop dimer using proteolytic footprinting. J Biol Chem. 1993;268:4227–4235
  42. Ungewickell E, Gratzer W. Self-association of human spectrin. A thermodynamic and kinetic study. Eur J Biochem. 1978;88:379–385
  43. Motulsky AG, Singer K, Crosby WH, et al.  The life span of the elliptocyte; hereditary elliptocytosis and its relationship to other familial hemolytic diseases. Blood. 1954;9:57–72
  44. Shahbakhti F, Gratzer WB. Analysis of the self-association of human red cell spectrin. Biochemistry. 1986;25:5969–5975
  45. Becker PS, Schwartz MA, Morrow JS, et al.  Radiolabel-transfer cross-linking demonstrates that protein 4.1 binds to the N-terminal region of beta spectrin and to actin in binary interactions. Eur J Biochem. 1990;193:827–836
  46. Bennett V, Baines AJ. Spectrin and ankyrin-based pathways (Metazoan inventions for integrating cells into tissues). Physiol Rev. 2001;81:1353–1392
  47. Gilligan DM, Bennett V. The junctional complex of the membrane skeleton. Semin Hematol. 1993;30:74–83
  48. Karinch AM, Zimmer WE, Goodman SR. The identification and sequence of the actin-binding domain of human red blood cell beta-spectrin. J Biol Chem. 1990;265:11833–11840
  49. McGough AM, Josephs R. On the structure of erythrocyte spectrin in partially expanded membrane skeletons. Proc Natl Acad Sci USA. 1990;87:5208–5212
  50. Morrow JS, Rimm DL, Kennedy SP, et al.  Of membrane stability and mosaics (The spectrin cytoskeleton). In:  Hoffman J,  Jamieson J editor. Handbook of Physiology. London, UK: Oxford University Press; 1997;p. 485–540
  51. Bresnick AR, Janmey PA, Condeelis J. Evidence that a 27-residue sequence is the actin-binding site of ABP-120. J Biol Chem. 1991;266:12989–12993
  52. Cohen CM, Tyler JM, Branton D. Spectrin-actin associations studied by electron microscopy of shadowed preparations. Cell. 1980;21:875–883
  53. De Matteis MA, Morrow JS. Spectrin tethers and mesh in the biosynthetic pathway. J Cell Sci. 2000;113:2331–2343
  54. Beaven GH, Jean-Baptiste L, Ungewickell E, et al.  An examination of the soluble oligomeric complexes extracted from the red cell membrane and their relation to the membrane cytoskeleton. Eur J Cell Biol. 1985;36:299–306
  55. Liu SC, Windisch P, Kim S, et al.  Oligomeric states of spectrin in normal erythrocyte membranes (Biochemical and electron microscopic studies). Cell. 1984;37:587–594
  56. Conboy JG, Chasis JA, Winardi R, et al.  An isoform-specific mutation in the protein 4.1 gene results in hereditary elliptocytosis and complete deficiency of protein 4.1 in erythrocytes but not in nonerythroid cells. J Clin Invest. 1993;91:77–82
  57. Delaunay J, Dhermy D. Mutations involving the spectrin heterodimer contact site (Clinical expression and alterations in specific function). Semin Hematol. 1993;30:21–33
  58. Giorgi M, Cianci CD, Gallagher PG, et al.  Spectrin oligomerization is cooperatively coupled to membrane assembly (A linkage targeted by many hereditary hemolytic anemias?). Exp Mol Pathol. 2001;70:215–230
  59. Burke JP, Van Zyl D, Zail SS, et al.  Reduced spectrin-ankyrin binding in a South African hereditary elliptocytosis kindred homozygous for spectrin St Claude. Blood. 1998;92:2591–2592
  60. Fournier CM, Nicolas G, Gallagher PG, et al.  Spectrin St Claude, a splicing mutation of the human alpha-spectrin gene associated with severe poikilocytic anemia. Blood. 1997;89:4584–4590
  61. Cabral WA, Mertts MV, Makareeva E, et al.  Type I collagen triplet duplication mutation in lethal osteogenesis imperfecta shifts register of alpha chains throughout the helix and disrupts incorporation of mutant helices into fibrils and extracellular matrix. J Biol Chem. 2003;278:10006–10012
  62. Liu SC, Derick LH, Palek J. Dependence of the permanent deformation of red blood cell membranes on spectrin dimer-tetramer equilibrium (Implication for permanent membrane deformation of irreversibly sickled cells). Blood. 1993;81:522–528
  63. Mohandas N, Chasis JA. Red blood cell deformability, membrane material properties and shape (Regulation by transmembrane, skeletal and cytosolic proteins and lipids). Semin Hematol. 1993;30:171–192
  64. Rebuck JW, Van Slyck EJ. An unsuspected ultrastructural fault in human elliptocytes. Am J Clin Pathol. 1968;49:19–25
  65. Florman AL, Wintrobe MM. Human elliptical red corpuscles. Bull Johns Hopkins Hosp. 1938;63:209–220
  66. Mohandas N, Clark MR, Health BP, et al.  A technique to detect reduced mechanical stability of red cell membranes (Relevance to elliptocytic disorders). Blood. 1982;59:768–774
  67. Mohandas N, Clark MR, Jacobs MS, et al.  Analysis of factors regulating erythrocyte deformability. J Clin Invest. 1980;66:563–573
  68. Chasis JA, Mohandas N. Erythrocyte membrane deformability and stability (Two distinct membrane properties that are independently regulated by skeletal protein associations). J Cell Biol. 1986;103:343–350
  69. Clark MR, Mohandas N, Shohet SB. Osmotic gradient ektacytometry (Comprehensive characterization of red cell volume and surface maintenance). Blood. 1983;61:899–910
  70. Johnson RM, Ravindranath Y. Osmotic scan ektacytometry in clinical diagnosis. J Pediatr Hematol Oncol. 1996;18:122–129
  71. Ham TH, Sayre RW, Dunn RF, et al.  Physical properties of red cells as related to effects in vivo. II. Effect of thermal treatment on rigidity of red cells, stroma and the sickle cell. Blood. 1968;32:862–871
  72. Chang K, Williamson JR, Zarkowsky HS. Effect of heat on the circular dichroism of spectrin in hereditary pyropoikilocytosis. J Clin Invest. 1979;64:326–328
  73. Ham TH, Shen SC, Fleming EM, et al.  Studies on the destruction of red blood cells: IV. Thermal injury: Action of heat in causing increased spheroidicity, osmotic and mechanical fragilities and hemolysis of erythrocytes: Observations on the mechanisms of destruction in such erythrocytes in dogs and in a patient with a fatal thermal burn. Blood. 1948;3:373–403
  74. Knowles WJ, Morrow JS, Speicher DW, et al.  Molecular and functional changes in spectrin from patients with hereditary pyropoikilocytosis. J Clin Invest. 1983;71:1867–1877
  75. Liu SC, Palek J, Prchal J, et al.  Altered spectrin dimer-dimer association and instability of erythrocyte membrane skeletons in hereditary pyropoikilocytosis. J Clin Invest. 1981;68:597–605
  76. Liu SC, Palek J, Prchal JT. Defective spectrin dimer-dimer association with hereditary elliptocytosis. Proc Natl Acad Sci USA. 1982;79:2072–2076
  77. Shotton DM, Burke BE, Branton D. The molecular structure of human erythrocyte spectrin. Biophysical and electron microscopic studies. J Mol Biol. 1979;131:303–329
  78. Speicher DW, Morrow JS, Knowles WJ, et al.  A structural model of human erythrocyte spectrin. Alignment of chemical and functional domains. J Biol Chem. 1982;257:9093–9101
  79. Speicher DW, Morrow JS, Knowles WJ, et al.  Identification of proteolytically resistant domains of human erythrocyte spectrin. Proc Natl Acad Sci USA. 1980;77:5673–5677
  80. Marchesi SL, Knowles WJ, Morrow JS, et al.  Abnormal spectrin in hereditary elliptocytosis. Blood. 1986;67:141–151
  81. Tse WT, Lecomte MC, Costa FF, et al.  Point mutation in the beta-spectrin gene associated with alpha I/74 hereditary elliptocytosis. Implications for the mechanism of spectrin dimer self-association. J Clin Invest. 1990;86:909–916
  82. Djinovic-Carugo K, Gautel M, Ylanne J, et al.  The spectrin repeat (A structural platform for cytoskeletal protein assemblies). FEBS Lett. 2002;513:119–123
  83. Nicolas G, Pedroni S, Fournier C, et al.  Spectrin self-association site (Characterization and study of beta-spectrin mutations associated with hereditary elliptocytosis). Biochem J. 1998;332:81–89
  84. Park S, Johnson ME, Fung LW. Nuclear magnetic resonance studies of mutations at the tetramerization region of human alpha spectrin. Blood. 2002;100:283–288
  85. Zhang Z, Weed SA, Gallagher PG, et al.  Dynamic molecular modeling of pathogenic mutations in the spectrin self- association domain. Blood. 2001;98:1645–1653
  86. Coetzer TL, Palek J. Partial spectrin deficiency in hereditary pyropoikilocytosis. Blood. 1986;67:919–924
  87. Luo BH, Mehboob S, Hurtuk MG, et al.  Important region in the beta-spectrin C-terminus for spectrin tetramer formation. Eur J Haematol. 2002;68:73–79
  88. Gallagher PG, Petruzzi MJ, Weed SA, et al.  Mutation of a highly conserved residue of betaI spectrin associated with fatal and near-fatal neonatal hemolytic anemia. J Clin Invest. 1997;99:267–277
  89. Gallagher PG, Weed SA, Tse WT, et al.  Recurrent fatal hydrops fetalis associated with a nucleotide substitution in the erythrocyte beta-spectrin gene. J Clin Invest. 1995;95:1174–1182
  90. Jarolim P, Wichterle H, Hanspal M, et al.  Beta spectrin PRAGUE (A truncated beta spectrin producing spectrin deficiency, defective spectrin heterodimer self-association and a phenotype of spherocytic elliptocytosis). Br J Haematol. 1995;91:502–510
  91. Dhermy D, Galand C, Bournier O, et al.  Coinheritance of alpha- and beta-spectrin gene mutations in a case of hereditary elliptocytosis. Blood. 1998;92:4481–4482
  92. Grum VL, Li D, MacDonald RI, et al.  Structures of two repeats of spectrin suggest models of flexibility. Cell. 1999;98:523–535
  93. Yan Y, Winograd E, Viel A, et al.  Crystal structure of the repetitive segments of spectrin. Science. 1993;262:2027–2030
  94. Dhermy D, Garbarz M, Lecomte MC, et al.  Abnormal electrophoretic mobility of spectrin tetramers in hereditary elliptocytosis. Hum Genet. 1986;74:363–367
  95. Guetarni D, Roux AF, Alloisio N, et al.  Evidence that expression of Sp alpha I/65 hereditary elliptocytosis is compounded by a genetic factor that is linked to the homologous alpha-spectrin allele. Hum Genet. 1990;85:627–630
  96. Lawler J, Coetzer TL, Palek J, et al.  Sp alpha I/65 (A new variant of the alpha subunit of spectrin in hereditary elliptocytosis). Blood. 1985;66:706–709
  97. Lecomte MC, Dhermy D, Solis C, et al.  A new abnormal variant of spectrin in black patients with hereditary elliptocytosis. Blood. 1985;65:1208–1217
  98. Roux AF, Morle F, Guetarni D, et al.  Molecular basis of Sp alpha I/65 hereditary elliptocytosis in North Africa (Insertion of a TTG triplet between codons 147 and 149 in the alpha-spectrin gene from five unrelated families). Blood. 1989;73:2196–2201
  99. Alloisio N, Morle L, Pothier B, et al.  Spectrin Oran (alpha II/21), a new spectrin variant concerning the alpha II domain and causing severe elliptocytosis in the homozygous state. Blood. 1988;71:1039–1047
  100. Alloisio N, Wilmotte R, Marechal J, et al.  A splice site mutation of alpha-spectrin gene causing skipping of exon 18 in hereditary elliptocytosis. Blood. 1993;81:2791–2798
  101. Alloisio N, Wilmotte R, Morle L, et al.  Spectrin Jendouba (An alpha II/31 spectrin variant that is associated with elliptocytosis and carries a mutation distant from the dimer self-association site). Blood. 1992;80:809–815
  102. Mootien S, Gallagher PG. Hereditary pyropoikilocytosis and the spectrinSt. Claude allele. Br J Haematol. 2004;124:251–252
  103. Johnson RM, Ravindranath Y, Brohn F, et al.  A large erythroid spectrin beta-chain variant. Br J Haematol. 1992;80:6–14
  104. Pranke PH, Basseres DS, Costa FF, et al.  Expression of spectrin alpha I/65 hereditary elliptocytosis in patients from Brazil. Br J Haematol. 1996;94:470–475
  105. Alloisio N, Morle L, Marechal J, et al.  Sp alpha V/41: A common spectrin polymorphism at the alpha IV-alpha V domain junction. Relevance to the expression level of hereditary elliptocytosis due to alpha-spectrin variants located in trans. J Clin Invest. 1991;87:2169–2177
  106. Wilmotte R, Marechal J, Delaunay J. Mutation at position −12 of intron 45 (c→t) plays a prevalent role in the partial skipping of exon 46 from the transcript of allele alphaLELY in erythroid cells. Br J Haematol. 1999;104:855–859
  107. Wilmotte R, Marechal J, Morle L, et al.  Low expression allele alpha LELY of red cell spectrin is associated with mutations in exon 40 (alpha V/41 polymorphism) and intron 45 and with partial skipping of exon 46. J Clin Invest. 1993;91:2091–2096
  108. Marechal J, Wilmotte R, Kanzaki A, et al.  Ethnic distribution of allele alpha LELY, a low-expression allele of red-cell spectrin alpha-gene. Br J Haematol. 1995;90:553–556
  109. Wilmotte R, Harper SL, Ursitti JA, et al.  The exon 46-encoded sequence is essential for stability of human erythroid alpha-spectrin and heterodimer formation. Blood. 1997;90:4188–4196
  110. Hanspal M, Hanspal JS, Kalraiya R, et al.  Asynchronous synthesis of membrane skeletal proteins during terminal maturation of murine erythroblasts. Blood. 1992;80:530–539
  111. Hanspal M, Palek J. Synthesis and assembly of membrane skeletal proteins in mammalian red cell precursors. J Cell Biol. 1987;105:1417–1424
  112. Basseres DS, Pranke PH, Vicentim D, et al.  Expression of spectrin alphaI/50 hereditary elliptocytosis and its association with the alphaLELY allele. Acta Haematol. 1998;100:32–38
  113. Gallagher PG, Forget BG. Spectrin St Louis and the alpha LELY allele. Blood. 1994;84:1686–1687
  114. Gallagher PG, Tse WT, Marchesi SL, et al.  A defect in alpha-spectrin mRNA accumulation in hereditary pyropoikilocytosis. Trans Assoc Am Physicians. 1991;104:32–39
  115. Hanspal M, Hanspal JS, Sahr KE, et al.  Molecular basis of spectrin deficiency in hereditary pyropoikilocytosis. Blood. 1993;82:1652–1660
  116. Conboy JG. Structure, function, and molecular genetics of erythroid membrane skeletal protein 4.1 in normal and abnormal red blood cells. Semin Hematol. 1993;30:58–73
  117. Hoover KB, Bryant PJ. The genetics of the protein 4.1 family (Organizers of the membrane and cytoskeleton). Curr Opin Cell Biol. 2000;12:229–234
  118. Leto TL, Marchesi VT. A structural model of human erythrocyte protein 4.1. J Biol Chem. 1984;259:4603–4608
  119. Takakuwa Y. Regulation of red cell membrane protein interactions (Implications for red cell function). Curr Opin Hematol. 2001;8:80–84
  120. Becker PS, Tse WT, Lux SE, et al.  Beta spectrin Kissimmee (A spectrin variant associated with autosomal dominant hereditary spherocytosis and defective binding to protein 4.1). J Clin Invest. 1993;92:612–616
  121. Coleman TR, Harris AS, Mische SM, et al.  Beta spectrin bestows protein 4.1 sensitivity on spectrin-actin interactions. J Cell Biol. 1987;104:519–526
  122. Conboy JG, Shitamoto R, Parra M, et al.  Hereditary elliptocytosis due to both qualitative and quantitative defects in membrane skeletal protein 4.1. Blood. 1991;78:2438–2443
  123. Correas I, Speicher DW, Marchesi VT. Structure of the spectrin-actin binding site of erythrocyte protein 4.1. J Biol Chem. 1986;261:13362–13366
  124. Correas I, Leto TL, Speicher DW, et al.  Identification of the functional site of erythrocyte protein 4.1 involved in spectrin-actin associations. J Biol Chem. 1986;261:3310–3315
  125. Discher DE, Winardi R, Schischmanoff PO, et al.  Mechanochemistry of protein 4.1’s spectrin-actin-binding domain (Ternary complex interactions, membrane binding, network integration, structural strengthening). J Cell Biol. 1995;130:897–907
  126. Han BG, Nunomura W, Takakuwa Y, et al.  Protein 4.1R core domain structure and insights into regulation of cytoskeletal organization. Nat Struct Biol. 2000;7:871–875
  127. Ohanian V, Wolfe LC, John KM, et al.  Analysis of the ternary interaction of the red cell membrane skeletal proteins spectrin, actin, and 4.1. Biochemistry. 1984;23:4416–4420
  128. Schischmanoff PO, Winardi R, Discher DE, et al.  Defining of the minimal domain of protein 4.1 involved in spectrin-actin binding. J Biol Chem. 1995;270:21243–21250
  129. Ungewickell E, Bennett PM, Calvert R, et al.  In vitro formation of a complex between cytoskeletal proteins of the human erythrocyte. Nature. 1979;280:811–814
  130. Workman RF, Low PS. Biochemical analysis of potential sites for protein 4.1-mediated anchoring of the spectrin-actin skeleton to the erythrocyte membrane. J Biol Chem. 1998;273:6171–6176
  131. Chasis JA, Coulombel L, Conboy J, et al.  Differentiation-associated switches in protein 4.1 expression. Synthesis of multiple structural isoforms during normal human erythropoiesis. J Clin Invest. 1993;91:329–338
  132. Conboy JG, Chan JY, Chasis JA, et al.  Tissue- and development-specific alternative RNA splicing regulates expression of multiple isoforms of erythroid membrane protein 4.1. J Biol Chem. 1991;266:8273–8280
  133. Conboy JG, Chan J, Mohandas N, et al.  Multiple protein 4.1 isoforms produced by alternative splicing in human erythroid cells. Proc Natl Acad Sci USA. 1988;85:9062–9065
  134. Gascard P, Lee G, Coulombel L, et al.  Characterization of multiple isoforms of protein 4.1R expressed during erythroid terminal differentiation. Blood. 1998;92:4404–4414
  135. Hou VC, Conboy JG. Regulation of alternative pre-mRNA splicing during erythroid differentiation. Curr Opin Hematol. 2001;8:74–79
  136. Huang JP, Tang CJ, Kou GH, et al.  Genomic structure of the locus encoding protein 4.1. Structural basis for complex combinational patterns of tissue-specific alternative RNA splicing. J Biol Chem. 1993;268:3758–3766
  137. Tang TK, Qin Z, Leto T, et al.  Heterogeneity of mRNA and protein products arising from the protein 4.1 gene in erythroid and nonerythroid tissues. J Cell Biol. 1990;110:617–624
  138. Chasis JA, Coulombel L, McGee S, et al.  Differential use of protein 4.1 translation initiation sites during erythropoiesis (Implications for a mutation-induced stage-specific deficiency of protein 4.1 during erythroid development). Blood. 1996;87:5324–5331
  139. Hou VC, Lersch R, Gee SL, et al.  Decrease in hnRNP A/B expression during erythropoiesis mediates a pre-mRNA splicing switch. EMBO J. 2002;21:6195–6204
  140. Winardi R, Discher D, Kelley C, et al.  Evolutionarily conserved alternative pre-mRNA splicing regulates structure and function of the spectrin-actin binding domain of erythroid protein 4.1. Blood. 1995;86:4315–4322
  141. Baklouti F, Huang SC, Tang TK, et al.  Asynchronous regulation of splicing events within protein 4.1 pre-mRNA during erythroid differentiation. Blood. 1996;87:3934–3941
  142. Deguillien M, Huang SC, Moriniere M, et al.  Multiple cis elements regulate an alternative splicing event at 4.1R pre-mRNA during erythroid differentiation. Blood. 2001;98:3809–3816
  143. Gee SL, Aoyagi K, Lersch R, et al.  Alternative splicing of protein 4.1R exon 16 (ordered excision of flanking introns ensures proper splice site choice). Blood. 2000;95:692–699
  144. Huang SC, Liu ES, Cheng H. Comparative analysis of cis-elements regulation protein 4.1R exon 16 splicing in cells that predominantly include or exclude exon 16 in vivo. Blood. 2002;110:223a; (abstr)
  145. Ponthier JL, Chen WC, Gee SL, et al.  Positive regulation of protein 4.1R exon 16 alternative splicing may be mediated by interaction of HRNbp with intronic enhancers. Blood. 2002;110:222a; (abstr)
  146. Dhermy D, Garbarz M, Lecomte MC, et al.  Hereditary elliptocytosis (Clinical, morphological and biochemical studies of 38 cases). Nouv Rev Fr Hematol. 1986;28:129–140
  147. Feddal S, Brunet G, Roda L, et al.  Molecular analysis of hereditary elliptocytosis with reduced protein 4.1 in the French Northern Alps. Blood. 1991;78:2113–2119
  148. Feo CJ, Fischer S, Piau JP, et al.  1st instance of the absence of an erythrocyte membrane protein (band 4(1)) in a case of familial elliptocytic anemia. Nouv Rev Fr Hematol. 1980;22:315–325
  149. Lambert S, Zail S. Partial deficiency of protein 4.1 in hereditary elliptocytosis. Am J Hematol. 1987;26:263–272
  150. Dalla Venezia N, Gilsanz F, Alloisio N, et al.  Homozygous 4.1(-) hereditary elliptocytosis associated with a point mutation in the downstream initiation codon of protein 4.1 gene. J Clin Invest. 1992;90:1713–1717
  151. Tchernia G, Mohandas N, Shohet SB. Deficiency of skeletal membrane protein band 4.1 in homozygous hereditary elliptocytosis. Implications for erythrocyte membrane stability. J Clin Invest. 1981;68:454–460
  152. Takakuwa Y, Tchernia G, Rossi M, et al.  Restoration of normal membrane stability to unstable protein 4.1-deficient erythrocyte membranes by incorporation of purified protein 4.1. J Clin Invest. 1986;78:80–85
  153. Alloisio N, Dalla Venezia N, Rana A, et al.  Evidence that red blood cell protein p55 may participate in the skeleton-membrane linkage that involves protein 4.1 and glycophorin C. Blood. 1993;82:1323–1327
  154. Lambert S, Conboy J, Zail S. A molecular study of heterozygous protein 4.1 deficiency in hereditary elliptocytosis. Blood. 1988;72:1926–1929
  155. Rybicki AC, Heath R, Lubin B, et al.  Human erythrocyte protein 4.1 is a phosphatidylserine binding protein. J Clin Invest. 1988;81:255–260
  156. Sondag D, Alloisio N, Blanchard D, et al.  Gerbich reactivity in 4.1 (-) hereditary elliptocytosis and protein 4.1 level in blood group Gerbich deficiency. Br J Haematol. 1987;65:43–50
  157. Yawata A, Kanzaki A, Gilsanz F, et al.  A markedly disrupted skeletal network with abnormally distributed intramembrane particles in complete protein 4.1-deficient red blood cells (allele 4.1 Madrid) (Implications regarding a critical role of protein 4.1 in maintenance of the integrity of the red blood cell membrane). Blood. 1997;90:2471–2481
  158. Conboy J, Mohandas N, Tchernia G, et al.  Molecular basis of hereditary elliptocytosis due to protein 4.1 deficiency. N Engl J Med. 1986;315:680–685
  159. Garbarz M, Devaux I, Bournier O, et al.  Protein 4.1 Lille, a novel mutation in the downstream initiation codon of protein 4.1 gene associated with heterozygous 4,1(-) hereditary elliptocytosis. Hum Mutat. 1995;5:339–340
  160. Conboy J, Marchesi S, Kim R, et al.  Molecular analysis of insertion/deletion mutations in protein 4.1 in elliptocytosis. II. Determination of molecular genetic origins of rearrangements. J Clin Invest. 1990;86:524–530
  161. Marchesi SL, Conboy J, Agre P, et al.  Molecular analysis of insertion/deletion mutations in protein 4.1 in elliptocytosis. I. Biochemical identification of rearrangements in the spectrin/actin binding domain and functional characterizations. J Clin Invest. 1990;86:516–523
  162. Moriniere M, Ribeiro L, Dalla Venezia N, et al.  Elliptocytosis in patients with C-terminal domain mutations of protein 4.1 correlates with encoded messenger RNA levels rather than with alterations in primary protein structure. Blood. 2000;95:1834–1841
  163. Venezia ND, Maillet P, Morle L, et al.  A large deletion within the protein 4.1 gene associated with a stable truncated mRNA and an unaltered tissue-specific alternative splicing. Blood. 1998;91:4361–4367
  164. Alloisio N, Guetarni D, Morle L, et al.  Sp alpha I/65 hereditary elliptocytosis in North Africa. Am J Hematol. 1986;23:113–122
  165. Garrido-Lecca G, Luna G, Merino C. Hereditary elliptocytosis in a Peruvian family. N Engl J Med. 1957;256:311–314
  166. Geerdink RA, Helleman PW, Verloop MC. Hereditary elliptocytosis and hyperhaemolysis. A comparative study of 6 families with 145 patients. Acta Med Scand. 1966;179:715–728
  167. Jensson O, Jonasson T, Olafsson O. Hereditary elliptocytosis in Iceland. Br J Haematol. 1967;13:844–854
  168. Lecomte MC, Dhermy D, Garbarz M, et al.  Hereditary elliptocytosis with a spectrin molecular defect in a white patient. Acta Haematol. 1984;71:235–240
  169. Morle L, Alloisio N, Ducluzeau MT, et al.  Spectrin Tunis (alpha I/78) (A new alpha I variant that causes asymptomatic hereditary elliptocytosis in the heterozygous state). Blood. 1988;71:508–511
  170. Morle L, Morle F, Roux AF, et al.  Spectrin Tunis (Sp alpha I/78), an elliptocytogenic variant, is due to the CGG→TGG codon change (Arg→Trp) at position 35 of the alpha I domain. Blood. 1989;74:828–832
  171. Pothier B, Alloisio N, Marechal J, et al.  Assignment of Sp alpha I/74 hereditary elliptocytosis to the alpha- or beta-chain of spectrin through in vitro dimer reconstitution. Blood. 1990;75:2061–2069
  172. Dalla Venezia N, Wilmotte R, Morle L, et al.  An alpha-spectrin mutation responsible for hereditary elliptocytosis associated in cis with the alpha v/41 polymorphism. Hum Genet. 1993;90:641–644
  173. Lawler J, Liu SC, Palek J, et al.  Molecular defect of spectrin in hereditary pyropoikilocytosis. Alterations in the trypsin-resistant domain involved in spectrin self-association. J Clin Invest. 1982;70:1019–1030
  174. Mentzer WC, Turetsky T, Mohandas N, et al.  Identification of the hereditary pyropoikilocytosis carrier state. Blood. 1984;63:1439–1446
  175. Palek J. Hereditary elliptocytosis and related disorders. Clin Haematol. 1985;14:45–87
  176. Kruatrachue M, Asawapokee N. Hereditary elliptocytosis and Plasmodium falciparum malaria. Ann Trop Med Parasitol. 1972;66:161–162
  177. Nkrumah FK. Hereditary elliptocytosis associated with severe haemolytic anaemia and malaria. Afr J Med Sci. 1972;3:131–136
  178. Ozer L, Mills GC. Elliptocytosis with haemolytic anaemia. Br J Haematol. 1964;10:468–476
  179. Jarolim P, Palek J, Coetzer TL, et al.  Severe hemolysis and red cell fragmentation caused by the combination of a spectrin mutation with a thrombotic microangiopathy. Am J Hematol. 1989;32:50–56
  180. Garbarz M, Lecomte MC, Feo C, et al.  Hereditary pyropoikilocytosis and elliptocytosis in a white French family with the spectrin alpha I/74 variant related to a CGT to CAT codon change (Arg to His) at position 22 of the spectrin alpha I domain. Blood. 1990;75:1691–1698
  181. Lawler J, Liu SC, Palek J, et al.  A molecular defect of spectrin in a subset of patients with hereditary elliptocytosis. Alterations in the alpha-subunit domain involved in spectrin self-association. J Clin Invest. 1984;73:1688–1695
  182. Lecomte MC, Feo C, Gautero H, et al.  Severe recessive poikilocytic anaemia with a new spectrin alpha chain variant. Br J Haematol. 1990;74:497–507
  183. Baklouti F, Marechal J, Wilmotte R, et al.  Elliptocytogenic alpha I/36 spectrin Sfax lacks nine amino acids in helix 3 of repeat 4. Evidence for the activation of a cryptic 5′-splice site in exon 8 of spectrin alpha-gene. Blood. 1992;79:2464–2470
  184. Baklouti F, Marechal J, Morle L, et al.  Occurrence of the alpha I 22 Arg→His (CGT→CAT) spectrin mutation in Tunisia (potential association with severe elliptopoikilocytosis). Br J Haematol. 1991;78:108–113
  185. Dalla Venezia N, Alloisio N, Forissier A, et al.  Elliptopoikilocytosis associated with the alpha 469 His→Pro mutation in spectrin Barcelona (alpha I/50–46b). Blood. 1993;82:1661–1665
  186. Gallagher PG, Lux SE. Disorders of the erythrocyte membrane. In:  Nathan DG,  Orkin SH editor. Hematology of Infancy and Childhood. Philadelphia, PA: Saunders; 2003;p. 560–684
  187. Dhermy D, Lecomte MC, Garbarz M, et al.  Molecular defect of spectrin in the family of a child with congenital hemolytic poikilocytic anemia. Pediatr Res. 1984;18:1005–1012
  188. Evans JP, Baines AJ, Hann IM, et al.  Detective spectrin dimer-dimer association in a family with transfusion-dependent homozygous hereditary elliptocytosis. Br J Haematol. 1983;54:163–172
  189. Garbarz M, Lecomte MC, Dhermy D, et al.  Double inheritance of an alpha I/65 spectrin variant in a child with homozygous elliptocytosis. Blood. 1986;67:1661–1667
  190. Grech JL, Cachia EA, Calleja F, et al.  Hereditary elliptocytosis in two Maltese families. J Clin Pathol. 1961;14:365–373
  191. Haddy TB, Rana SR. Homozygous hereditary elliptocytosis with hemolytic anemia. South Med J. 1984;77:631–633
  192. Iarocci TA, Wagner GM, Mohandas N, et al.  Hereditary poikilocytic anemia associated with the co-inheritance of two alpha spectrin abnormalities. Blood. 1988;71:1390–1396
  193. Lawler J, Coetzer TL, Mankad VN, et al.  Spectrin-alpha I/61 (A new structural variant of alpha-spectrin in a double-heterozygous form of hereditary pyropoikilocytosis). Blood. 1988;72:1412–1415
  194. Lecomte MC, Feo C. Severe hereditary elliptocytosis in two related Caucasian children with a decreased amount of spectrin (Sp) α chain. J Cell Biol. 1989;13B:230; (abstr)
  195. Lipton EL. Elliptocytosis with hemolytic anemia (The effects of splenectomy). Pediatrics. 1955;15:67–83
  196. Nielsen JA, Praktitioner S. Homozygous hereditary elliptocytosis as the cause of haemolytic anemia in infancy. Scand J Haematol. 1968;5:486–496
  197. Pryor DS, Pitney WR. Hereditary elliptocytosis (A report of two families from new guinea). Br J Haematol. 1967;13:126–134
  198. Dacie JV, Mollison PL, Richardson N, et al.  Atypical congenital haemolytic anaemia. Q J Med. 1953;22:79–98
  199. DePalma L, Luban NL. Hereditary pyropoikilocytosis. Clinical and laboratory analysis in eight infants and young children. Am J Dis Child. 1993;147:93–95
  200. Floyd PB, Gallagher PG, Valentino LA, et al.  Heterogeneity of the molecular basis of hereditary pyropoikilocytosis and hereditary elliptocytosis associated with increased levels of the spectrin alpha I/74-kilodalton tryptic peptide. Blood. 1991;78:1364–1372
  201. Prchal JT, Castleberry RP, Parmley RT, et al.  Hereditary pyropoikilocytosis and elliptocytosis (Clinical, laboratory, and ultrastructural features in infants and children). Pediatr Res. 1982;16:484–489
  202. Wiley JS, Gill FM. Red cell calcium leak in congenital hemolytic anemia with extreme microcytosis. Blood. 1976;47:197–210
  203. Zarkowsky HS. Heat-induced erythrocyte fragmentation in neonatal elliptocytosis. Br J Haematol. 1979;41:515–518
  204. Zarkowsky HS, Mohandas N, Speaker CB, et al.  A congenital haemolytic anaemia with thermal sensitivity of the erythrocyte membrane. Br J Haematol. 1975;29:537–543
  205. Austin RF, Desforges JF. Hereditary elliptocytosis (An unusual presentation of hemolysis in the newborn associated with transient morphologic abnormalities). Pediatrics. 1969;44:196–200
  206. Carpentieri U, Gustavson LP, Haggard ME. Pyknocytosis in a neonate (An unusual presentation of hereditary elliptocytosis). Clin Pediatr (Phila). 1977;16:76–78
  207. Josephs HW, Avery ME. Hereditary elliptocytosis associated with increased hemolysis. Pediatrics. 1955;16:741–752
  208. Lane PA, Shew RL, Iarocci TA, et al.  Unique alpha-spectrin mutant in a kindred with common hereditary elliptocytosis. J Clin Invest. 1987;79:989–996
  209. Lecomte MC, Garbarz M, Grandchamp B, et al.  Sp alpha I/78 (A mutation of the alpha I spectrin domain in a white kindred with HE and HPP phenotypes). Blood. 1989;74:1126–1133
  210. Manno S, Takakuwa Y, Nagao K, et al.  Modulation of erythrocyte membrane mechanical function by beta-spectrin phosphorylation and dephosphorylation. J Biol Chem. 1995;270:5659–5665
  211. Mentzer WC, Iarocci TA, Mohandas N, et al.  Modulation of erythrocyte membrane mechanical stability by 2,3-diphosphoglycerate in the neonatal poikilocytosis/elliptocytosis syndrome. J Clin Invest. 1987;79:943–949
  212. Jankovic M, Sansone G, Conter V, et al.  Atypical hereditary ovalocytosis associated with defective dyserythropoietic anemia. Acta Haematol. 1993;89:35–37
  213. Torlontano G, Fioritoni G, Salvati AM. Hereditary haemolytic ovalocytosis with defective erythropoiesis. Br J Haematol. 1979;43:435–441
  214. Cutting HO, McHugh WJ, Conrad FG, et al.  Autosomal dominant hemolytic anemia characterized by ovalocytosis; a family study of seven involved members. Am J Med. 1965;39:21–34
  215. Dacie JV. Hereditary elliptocytosis (HE). In: (ed 3). The Haemolytic Anaemias. vol 1:Edinburg, UK: Churchill Livingstone; 1985;p. 216–258
  216. Flint A. Elliptical human erythrocytes. Science. 1904;19:796
  217. Weiss HJ. Hereditary elliptocytosis with hemolytic anemia. Report of six cases. Am J Med. 1963;35:455–466
  218. Griffin HZ, Watkins CH. Ovalocytosis with features of hemolytic icterus. Trans Assoc Am Physicians. 1939;54:355
  219. Greenberg LH, Tanaka KR. Hereditary elliptocytosis with hemolytic anemia—A family study of five affected members. Calif Med. 1969;110:389–393
  220. Matsumoto N, Ishihara T, Takahashi M, et al.  Fine structures of the spleen in hereditary elliptocytosis. Acta Pathol Jpn. 1976;26:533–542
  221. Wilson HE, Long MJ. Hereditary ovalocytosis (elliptocytosis) with hypersplenism. Arch Intern Med. 1955;95:438–444
  222. Dahr W, Moulds J, Baumeister G, et al.  Altered membrane sialoglycoproteins in human erythrocytes lacking the Gerbich blood group antigens. Biol Chem Hoppe Seyler. 1985;366:201–211
  223. Daniels GL, Reid ME, Anstee DJ, et al.  Transient reduction in erythrocyte membrane sialoglycoprotein beta associated with the presence of elliptocytes. Br J Haematol. 1988;70:477–481
  224. Yawata Y, Kanzaki A, Yawata A. Genotypic and phenotypic expressions of protein 4.2 in human erythroid cells. Gene Funct Dis. 2000;2:61–81
  225. Breckenridge RL, Riggs JA. Hereditary elliptocytosis with hemolytic anemia complicating pregnancy. Am J Obstet Gynecol. 1968;101:861–862
  226. Emembolu JO, Mba EC. Red cell osmotic fragility in pregnant Nigerian women. Int J Gynaecol Obstet. 1994;44:73–74
  227. Pajor A, Lehoczky D. Hemolytic anemia precipitated by pregnancy in a patient with hereditary elliptocytosis. Am J Hematol. 1996;52:240–241
  228. Sahr KE, Coetzer TL, Moy LS, et al.  Spectrin cagliari. An Ala→Gly substitution in helix 1 of beta spectrin repeat 17 that severely disrupts the structure and self-association of the erythrocyte spectrin heterodimer. J Biol Chem. 1993;268:22656–22662
  229. Wandersee NJ, Roesch AN, Hamblen NR, et al.  Defective spectrin integrity and neonatal thrombosis in the first mouse model for severe hereditary elliptocytosis. Blood. 2001;97:543–550
  230. Wandersee NJ, Olson SC, Holzhauer SL, et al.  Increased erythrocyte adhesion in mice and humans with hereditary spherocytosis and hereditary elliptocytosis. Blood. 2004;103:710–716
  231. Shi ZT, Afzal V, Coller B, et al.  Protein 4.1R-deficient mice are viable but have erythroid membrane skeleton abnormalities. J Clin Invest. 1999;103:331–340
  232. Walensky LD, Shi ZT, Blackshaw S, et al.  Neurobehavioral deficits in mice lacking the erythrocyte membrane cytoskeletal protein 4.1. Curr Biol. 1998;8:1269–1272
  233. Liao EC, Paw BH, Peters LL, et al.  Hereditary spherocytosis in zebrafish riesling illustrates evolution of erythroid beta-spectrin structure, and function in red cell morphogenesis and membrane stability. Development. 2000;127:5123–5132
  234. Shafizadeh E, Paw BH, Foott H, et al.  Characterization of zebrafish merlot/chablis as non-mammalian vertebrate models for severe congenital anemia due to protein 4.1 deficiency. Development. 2002;129:4359–4370
  235. Dhermy D, Feo C, Garbarz M, et al.  Prenatal diagnosis of hereditary elliptocytosis with molecular defect of spectrin. Prenat Diagn. 1987;7:471–483
  236. Morris SA, Ohanian V, Lewis ML, et al.  Prenatal diagnosis of hereditary red cell membrane defect. Br J Haematol. 1986;62:763–772
  237. Boavida MG, Ambrosio P, Dhermy D, et al.  Isochromosome 14q in refractory anemia. Cancer Genet Cytogenet. 1997;97:155–156
  238. Djaldetti M, Cohen A, Hart J. Elliptocytosis preceding myelofibrosis in a patient with polycythemia vera. Acta Haematol. 1984;72:26–28
  239. Hartz JW, Buss DH, White DR, et al.  Marked elliptocytosis and schistocytosis in hematopoietic dysplasia. Am J Clin Pathol. 1984;82:354–359
  240. Rummens JL, Verfaillie C, Criel A, et al.  Elliptocytosis and schistocytosis in myelodysplasia (Report of two cases). Acta Haematol. 1986;75:174–177
  241. Ideguchi H, Yamada Y, Kondo S, et al.  Abnormal erythrocyte band 4.1 protein in myelodysplastic syndrome with elliptocytosis. Br J Haematol. 1993;85:387–392
  242. Kurtin PJ, Dewald GW, Shields DJ, et al.  Hematologic disorders associated with deletions of chromosome 20q (A clinicopathologic study of 107 patients). Am J Clin Pathol. 1996;106:680–688
  243. Gallagher PG, Kotula L, Wang Y, et al.  Molecular basis and haplotyping of the alphaII domain polymorphisms of spectrin (Application to the study of hereditary elliptocytosis and pyropoikilocytosis). Am J Hum Genet. 1996;59:351–359
  244. Chishti AH, Palek J, Fisher D, et al.  Reduced invasion and growth of Plasmodium falciparum into elliptocytic red blood cells with a combined deficiency of protein 4.1, glycophorin C, and p55. Blood. 1996;87:3462–3469
  245. Facer CA. Malaria, hereditary elliptocytosis, and pyropoikilocytosis. Lancet. 1989;1:897
  246. Schulman S, Roth EF, Cheng B, et al.  Growth of Plasmodium falciparum in human erythrocytes containing abnormal membrane proteins. Proc Natl Acad Sci USA. 1990;87:7339–7343
  247. Silveira P, Cynober T, Dhermy D, et al.  Red blood cell abnormalities in hereditary elliptocytosis and their relevance to variable clinical expression. Am J Clin Pathol. 1997;108:391–399
  248. Penfold J, Lipscomb JM. Elliptocytosis in man, associated with hereditary haemorrhagic telangiectasis. Q J Med. 1943;12:157
  249. Amato D, Booth PB. Hereditary ovalocytosis in Melanesians. P N G Med J. 1977;20:26–32
  250. Booth PB, Serjeantson S, Woodfield DG, et al.  Selective depression of blood group antigens associated with hereditary ovalocytosis among melanesians. Vox Sang. 1977;32:99–110
  251. Castelino D, Saul A, Myler P, et al.  Ovalocytosis in Papua New Guinea—Dominantly inherited resistance to malaria. Southeast Asian J Trop Med Public Health. 1981;12:549–555
  252. Cattani JA, Gibson FD, Alpers MP, et al.  Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea. Trans R Soc Trop Med Hyg. 1987;81:705–709
  253. Fix AG, Baer AS, Lie-Injo LE. The mode of inheritance of ovalocytosis/elliptocytosis in Malaysian Orang Asli families. Hum Genet. 1982;61:250–253
  254. Harrison KL, Collins KA, McKenna HW. Hereditary elliptical stomatocytosis (A case report). Pathology. 1976;8:307–311
  255. Honig GR, Lacson PS, Maurer HS. A new familial disorder with abnormal erythrocyte morphology and increased permeability of the erythrocytes to sodium and potassium. Pediatr Res. 1971;5:159–166
  256. Baer A, Lie-Injo LE, Welch QB, et al.  Genetic factors and malaria in the Temuan. Am J Hum Genet. 1976;28:179–188
  257. Coetzer TL, Beeton L, van Zyl D, et al.  Southeast Asian ovalocytosis in a South African kindred with hemolytic anemia. Blood. 1996;87:1656–1657
  258. Ravindranath Y, Goyette G, Johnson RM. Southeast Asian ovalocytosis in an African-American family. Blood. 1994;84:2823–2824 (letter)
  259. Liu SC, Jarolim P, Rubin HL, et al.  The homozygous state for the band 3 protein mutation in Southeast Asian Ovalocytosis may be lethal. Blood. 1994;84:3590–3591
  260. Mgone CS, Koki G, Paniu MM, et al.  Occurrence of the erythrocyte band 3 (AE1) gene deletion in relation to malaria endemicity in Papua New Guinea. Trans R Soc Trop Med Hyg. 1996;90:228–231
  261. Allen SJ, O’Donnell A, Alexander ND, et al.  Prevention of cerebral malaria in children in Papua New Guinea by southeast Asian ovalocytosis band 3. Am J Trop Med Hyg. 1999;60:1056–1060
  262. Bunyaratvej A, Butthep P, Kaewkettong P, et al.  Malaria protection in hereditary ovalocytosis (Relation to red cell deformability, red cell parameters and degree of ovalocytosis). Southeast Asian J Trop Med Public Health. 1997;28(suppl 3):38–42
  263. Foo LC, Rekhraj V, Chiang GL, et al.  Ovalocytosis protects against severe malaria parasitemia in the Malayan aborigines. Am J Trop Med Hyg. 1992;47:271–275
  264. Genton B, al-Yaman F, Mgone CS, et al.  Ovalocytosis and cerebral malaria. Nature. 1995;378:564–565
  265. Serjeantson S, Bryson K, Amato D, et al.  Malaria and hereditary ovalocytosis. Hum Genet. 1977;37:161–167
  266. Mohandas N, Lie-Injo LE, Friedman M, et al.  Rigid membranes of Malayan ovalocytes (A likely genetic barrier against malaria). Blood. 1984;63:1385–1392
  267. Schofield AE, Tanner MJ, Pinder JC, et al.  Basis of unique red cell membrane properties in hereditary ovalocytosis. J Mol Biol. 1992;223:949–958
  268. Saul A, Lamont G, Sawyer WH, et al.  Decreased membrane deformability in Melanesian ovalocytes from Papua New Guinea. J Cell Biol. 1984;98:1348–1354
  269. Schofield AE, Reardon DM, Tanner MJ. Defective anion transport activity of the abnormal band 3 in hereditary ovalocytic red blood cells. Nature. 1992;355:836–838
  270. Tanner MJ, Bruce L, Groves JD, et al.  The defective red cell anion transporter (band 3) in hereditary South East Asian ovalocytosis and the role of glycophorin A in the expression of band 3 anion transport activity in Xenopus oocytes. Biochem Soc Trans. 1992;20:542–546
  271. Kanki T, Young MT, Sakaguchi M, et al.  The N-terminal region of the transmembrane domain of human erythrocyte band 3. Residues critical for membrane insertion and transport activity. J Biol Chem. 2003;278:5564–5573
  272. Husain-Chishti A, Andrabi K. Altered tyrosine phosphorylation of the red cell band 3 protein in malaria resistant Southeast Asian ovalocytosis (SAO). Blood. 1991;78:80a; (abstr)
  273. Jones GL, Edmundson HM, Wesche D. Human erythrocyte band-3 has an altered N terminus in maleria-resistant Melanesian ovalocytosis. Biochim Biophys Acta. 1990;1096:33–40
  274. Liu SC, Zhai S, Palek J, et al.  Molecular defect of the band 3 protein in southeast Asian ovalocytosis. N Engl J Med. 1990;323:1530–1538
  275. Mohandas N, Winardi R, Knowles D, et al.  Molecular basis for membrane rigidity of hereditary ovalocytosis. A novel mechanism involving the cytoplasmic domain of band 3. J Clin Invest. 1992;89:686–692
  276. Kuma H, Inoue K, Fu G, et al.  Secondary structures of synthetic peptides corresponding to the first membrane-contact portion of normal band 3 and its deletion mutant (Southeast Asian ovalocytosis). J Biochem (Tokyo). 1998;124:509–518
  277. Chambers EJ, Bloomberg GB, Ring SM, et al.  Structural studies on the effects of the deletion in the red cell anion exchanger (band 3, AE1) associated with South East Asian ovalocytosis. J Mol Biol. 1999;285:1289–1307
  278. Liu SC, Palek J, Yi SJ, et al.  Molecular basis of altered red blood cell membrane properties in Southeast Asian ovalocytosis (role of the mutant band 3 protein in band 3 oligomerization and retention by the membrane skeleton). Blood. 1995;86:349–358
  279. Moriyama R, Ideguchi H, Lombardo CR, et al.  Structural and functional characterization of band 3 from Southeast Asian ovalocytes. J Biol Chem. 1992;267:25792–25797
  280. Jarolim P, Palek J, Amato D, et al.  Deletion in erythrocyte band 3 gene in malaria-resistant Southeast Asian ovalocytosis. Proc Natl Acad Sci USA. 1991;88:11022–11026
  281. Mueller TJ, Morrison M. Detection of a variant of protein 3, the major transmembrane protein of the human erythrocyte. J Biol Chem. 1977;252:6573–6576
  282. Jarolim P, Rubin HL, Zhai S, et al.  Band 3 Memphis (A widespread polymorphism with abnormal electrophoretic mobility of erythrocyte band 3 protein caused by substitution AAG→GAG (Lys→Glu) in codon 56). Blood. 1992;80:1592–1598
  283. Yannoukakos D, Vasseur C, Driancourt C, et al.  Human erythrocyte band 3 polymorphism (band 3 Memphis) (Characterization of the structural modification (Lys 56→Glu) by protein chemistry methods). Blood. 1991;78:1117–1120
  284. Laosombat V, Dissaneevate S, Peerapittayamongkol C, et al.  Neonatal hyperbilirubinemia associated with Southeast Asian ovalocytosis. Am J Hematol. 1999;60:136–139
  285. O’Donnell A, Allen SJ, Mgone CS, et al.  Red cell morphology and malaria anaemia in children with Southeast-Asian ovalocytosis band 3 in Papua New Guinea. Br J Haematol. 1998;101:407–412
  286. Bruce LJ, Wrong O, Toye AM, et al.  Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea (Loss of up to 95% band 3 transport in red cells). Biochem J. 2000;350:41–51
  287. Vasuvattakul S, Yenchitsomanus PT, Vachuanichsanong P, et al.  Autosomal recessive distal renal tubular acidosis associated with Southeast Asian ovalocytosis. Kidney Int. 1999;56:1674–1682
  288. Okoye VC, Bennett V. Plasmodium falciparum malaria (Band 3 as a possible receptor during invasion of human erythrocytes). Science. 1985;227:169–171
  289. Dluzewski AR, Fryer PR, Griffiths S, et al.  Red cell membrane protein distribution during malarial invasion. J Cell Sci. 1989;92:691–699
  290. Parquet N, Devaux I, Boulanger L, et al.  Identification of three novel spectrin alpha I/74 mutations in hereditary elliptocytosis (Further support for a triple-stranded folding unit model of the spectrin heterodimer contact site). Blood. 1994;84:303–308
  291. Gallagher PG, Zhang Z, Morrow JS, et al: Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the alphabeta spectrin self-association binding site. Lab Invest (in press)
  292. Perrotta S, Miraglia del Giudice E, Alloisio N, et al.  Mild elliptocytosis associated with the alpha 34 Arg→Trp mutation in spectrin Genova (alpha I/74). Blood. 1994;83:3346–3349
  293. Perrotta S, Iolascon A, De Angelis F, et al.  Spectrin Anastasia (alpha I/78) (A new spectrin variant (alpha 45 Arg→Thr) with moderate elliptocytogenic potential). Br J Haematol. 1995;89:933–936
  294. Morle L, Roux AF, Alloisio N, et al.  Two elliptocytogenic alpha I/74 variants of the spectrin alpha I domain. Spectrin Culoz (GGT→GTT; alpha I 40 Gly→Val) and spectrin Lyon (CTT→TTT; alpha I 43 Leu→Phe). J Clin Invest. 1990;86:548–554
  295. Boulanger L, Dhermy D, Garbarz M, et al.  A second allele of spectrin alpha-gene associated with the alpha I/65 phenotype (allele alpha Ponte de Sor). Blood. 1994;84:2056
  296. Hassoun H, Coetzer TL, Vassiliadis JN, et al.  A novel mobile element inserted in the alpha spectrin gene: Spectrin dayton. A truncated alpha spectrin associated with hereditary elliptocytosis. J Clin Invest. 1994;94:643–648
  297. Sahr KE, Tobe T, Scarpa A, et al.  Sequence and exon-intron organization of the DNA encoding the alpha I domain of human spectrin. Application to the study of mutations causing hereditary elliptocytosis. J Clin Invest. 1989;84:1243–1252
  298. Gallagher PG, Roberts WE, Benoit L, et al.  Poikilocytic hereditary elliptocytosis associated with spectrin Alexandria (An alpha I/50b Kd variant that is caused by a single amino acid deletion). Blood. 1993;82:2210–2215
  299. Garbarz M, Boulanger L, Pedroni S, et al.  Spectrin beta Tandil, a novel shortened beta-chain variant associated with hereditary elliptocytosis is due to a deletional frameshift mutation in the beta-spectrin gene. Blood. 1992;80:1066–1073
  300. Pothier B, Morle L, Alloisio N, et al.  Spectrin Nice (beta 220/216) (A shortened beta-chain variant associated with an increase of the alpha I/74 fragment in a case of elliptocytosis). Blood. 1987;69:1759–1765
  301. Tse WT, Gallagher PG, Pothier B, et al.  An insertional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin nice (beta 220/216). Blood. 1991;78:517–523
  302. Wilmotte R, Miraglia del Giudice E, Marechal J, et al.  A deletional frameshift mutation in spectrin beta-gene associated with hereditary elliptocytosis in spectrin Napoli. Br J Haematol. 1994;88:437–439
  303. Kanzaki A, Rabodonirina M, Yawata Y, et al.  A deletional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin Tokyo (beta 220/216). Blood. 1992;80:2115–2121
  304. Qualtieri A, Pasqua A, Bisconte MG, et al.  Spectrin Cosenza (A novel beta chain variant associated with Sp alphaI/74 hereditary elliptocytosis). Br J Haematol. 1997;97:273–278
  305. Maillet P, Inoue T, Kanzaki A, et al.  Stop codon in exon 30 (E2069X) of beta-spectrin gene associated with hereditary elliptocytosis in spectrin Nagoya. Hum Mutat. 1996;8:366–368
  306. Eber SW, Morris SA, Schroter W, et al.  Interactions of spectrin in hereditary elliptocytes containing truncated spectrin beta-chains. J Clin Invest. 1988;81:523–530
  307. Yoon SH, Yu H, Eber S, et al.  Molecular defect of truncated beta-spectrin associated with hereditary elliptocytosis. Beta-spectrin Gottingen. J Biol Chem. 1991;266:8490–8494
  308. Dhermy D, Lecomte MC, Garbarz M, et al.  Spectrin beta-chain variant associated with hereditary elliptocytosis. J Clin Invest. 1982;70:707–715
  309. Gallagher PG, Tse WT, Costa F, et al.  A splice site mutation of the beta-spectrin gene causing exon skipping in hereditary elliptocytosis associated with a truncated beta-spectrin chain. J Biol Chem. 1991;266:15154–15159
  310. Garbarz M, Tse WT, Gallagher PG, et al.  Spectrin Rouen (beta 220–218), a novel shortened beta-chain variant in a kindred with hereditary elliptocytosis. Characterization of the molecular defect as exon skipping due to a splice site mutation. J Clin Invest. 1991;88:76–81
  311. Lecomte MC, Gautero H, Bournier O, et al.  Elliptocytosis-associated spectrin Rouen (beta 220/218) has a truncated but still phosphorylatable beta chain. Br J Haematol. 1992;80:242–250
  312. Basseres DS, Pranke PH, Sales TS, et al.  Beta-spectrin Campinas (A novel shortened beta-chain variant associated with skipping of exon 30 and hereditary elliptocytosis). Br J Haematol. 1997;97:579–585

☆ Supported in part by grants from the National Institutes of Health and the March of Dimes Birth Defects Foundation.

PII: S0037-1963(04)00004-6

doi: 10.1053/j.seminhematol.2004.01.003

Seminars in Hematology
Volume 41, Issue 2 , Pages 142-164 , April 2004

Article Tools

* Image Usage & Resolution