Summary
αI/65 Hereditary elliptocytosis (HE) is due to the duplication of TTG codon 1541 (leucine) of α-spectrin and is associated with a constant haplotype. It was encountered exclusively in African and American Blacks, and in North Africans. We assumed that it diffused from the Benin-Togo area to Northern Africa. We now report two South Italian families with αI/65 HE. The phenotype fully conformed to previous descriptions. The mode of transmission was dominant; however, the manifestations were more pronounced when the common, low expression level αV/41 allele occurred in trans to the αI/65 allele, also conforming to previous records. The mutation underlying αI/65 HE turned out to be, again, the duplication of TTG codon 154 and the associated haplotype was the same as that encountered previously (+-+; XbaI, PvuII, MspI). Thus, the αI/65 allele found in Italy must have been introduced from North Africa across the Sicilian channel and would ultimately have originated from the Benin-Togo area. It would witness the same migratory stream as that followed by the Benin type haemoglobin S allele, which is also present in Southern Italy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alloisio N, Guertani D, Morlé L, Pothier B, Ducluzeau MT, Soun A, Colonna P, Clerc M, Philippe N, Delaunay J (1986) SpαI/65 hereditary elliptocytosis in North Africa. Am J Hematol 23:113–122
Alloisio N, Morlé L, Marechal J, Roux AF, Ducluzeau MT, Guetarni D, Pothier B, Baklouti F, Ghanem A, Kastally R, Delaunay J (1991) SpαV/41:a common spectrin polymorphism at the αIV-αV domain junction. Relevance to the expression level of hereditary elliptocytosis due to a spectrin variants located in trans. J Clin Invest 87:2169–2177
Beutler E (1991) Glucose-6-phosphate dehydrogenease deficiency. N Engl J Med 324:169–174
Coetzer T, Palek J, Lawler J, Liu SC, Jarolim P, Lahav M, Prchal JT, Wang W, Alter BP, Schewitz G, Mankad V, Galanello R, Cao A (1990) Structural and functional heterogeneity of alpha spectrin mutations involving the spectrin heterodimer self-association site: relationship to hematologic expression of homozygous hereditary elliptocytosis and hereditary pyropoikilocytosis. Blood 75:2235–2244
Delaunay J, Alloisio N, Morlé L, Pothier B (1990) The red cell skeleton and its genetic disorders. Mol Aspects Med 11:161–241
Gallagher PG, Tse WT, Forget BG (1990) Clinical and molecular aspects of disorders of the erythrocyte membrane. Semin Perinatol 14:351–367
Garbarz M, Lecomte MC, Dhermy D, Feo C, Chaveroche I, Gautero H, Bournier O, Picat C, Goepp A, Boivin P (1986) Double inheritance of an αI/65 spectrin variant in a child with homozygous elliptocytosis. Blood 67:1661–1667
Guetarni D, Roux AF, Alloisio N, Morlé F, Ducluzeau MT, Forget BG, Colonna P, Delaunay J, Godet J (1990) Evidence that expression of spectrin αI/65- hereditary elliptocytosis is compounded by a genetic factor that is linked to the homologous alpha spectrin allele. Hum Genet 85:627–630
Hoffman N, Stanislovitis P, Watkins PC, Klinger KW, Linnenbach AJ, Forget BG (1987) Three RFLPs are detected by an alpha spectrin genomic clone. Nucleic Acids Res 15:4696
Lawler J, Coetzer TL, Palek J, Jacob HS, Luban N (1985) SpαI/65: a new variant of a subunit in a double heterozygous form of hereditary pyropoikilocytosis. Blood 72:1412–1415
Lecomte MC, Dhermy D, Solis C, Ester A, Feo C, Gautero H, Bournier O, Boivin P (1985) A new abnormal variant of spectrin in black patients with hereditary elliptocytosis. Blood 65:208–1217
Lecomte MC, Dhermy D, Gautero H, Bournier O, Galand C, Boivin P (1988) L'elliptocytoses hereditaire en Afrique de l'Quest: frequence et repartition des variants de la spectrine. C R Acad Sci [III] 306:43–46
Linnenbach AJ, Speicher DW, Marchesi VT, Forget BG (1986) Cloning of a portion of the chromosomal gene for human erythrocyte alpha spectrin by using a synthetic gene fragment. Proc Natl Acad Sci 83:2397–2401
Marchesi SL, Letsinger JT, Speicher DW, Marchesi VT, Agre P, Hyun B, Gulati G (1987) Mutant forms of spectrin alpha subunits in hereditary elliptocytosis. J Clin Invest 80:191–198
Mears JG, Beldjord C, Benabadji M, Belghiti YA, Baddou MA, Labie D, Nagel RL (1981) Sickle gene polymorphism in North Africa. Blood 58:599–601
Pagnier J, Mears JG, Dunda-Belkodia I, Schaeffer-Rego KE, Belford G, Nagel RL, Labie D (1984) Evidence of the multicentric origin of the hemoglobin S gene in Africa. Proc Natl Acad Sci 81:1771–1773
Palek J, Lambert S (1990) Genetic of the red cell membrane skeleton. Semin Hematol 27:290–332
Ragusa A, Lombardo M, Sortino G, Lombardo T, Nagel RL, Labie D (1988) βS gene in Sicily is in linkage disequilibrium with the Benin haplotype: implications for gene flow disequilibrium. Am J Hematol 27:139–141
Roux AF, Morlé F, Guetarni D, Colonna P, Sahr K, Forget BG, Delaunay J, Godet J (1989) Molecular basis of Sp αI/65 hereditary elliptocytosis in North Africa: insertion of a TTG triplet between codons 147 and 149 in the α-spectrin gene from five unrelated families. Blood 73:2196–2201
Sahr KE, Tobe T, Scarpa A, Laughinhouse K, Marchesi SL, Agre P, Linnenbach AJ, Marchesi VT, Forget BG (1989) Sequence and exon intron organization of the DNA encoding the α-I domain of human spectrin. Application to the study of mutations causing hereditary elliptocytosis. J Clin Invest 84:1243–1252
Sahr KE, Garbarz M, Dhermy D, Lecomte MC, Boivin P, Agre P, Laughinghouse K, Scarpa A, Coetzer T, Palek J, Marchesi SL, Forget BG (1990) Use of the polymerase chain reaction for the detection and characterization of mutations causing hereditary elliptocytosis. In: Cohen CM, Palek J (eds) Cellular and molecular biology of normal and abnormal erythroid membranes, new series, vol 118. Liss, New York, pp 201–206
Sahr KE, Laurilla P, Kotula L, Scarpa AL, Coupal E, Leto TL, Linnenbach AJ, Winkelmann JC, Speicher DW, Marchesi VT, Curtis PJ, Forget BG (1990) The complete cDNA and polypeptide sequences of human erythroid α-spectrin. J Biol Chem 265:4434–4443
Sandler GS, Schilirò G, Russo A, Musumeci S, Rachmilewitz EA (1978) Blood group phenotypes and the origin of sickle cell hemoglobin in sicilians. Acta Haematol 60:350–357
Schilirò G, Romeo MA, Russo-Mancuso G, Samperi P, Russo A (1986) Hemoglobin C disorders in whites. Am J Med Genet 1:24–28
Schilirò G, Spena M, Giambelluca E, Maggio A (1990) Sickle hemoglobinopathies in Sicily. Am J Hematol 33:81–85
Schulman S, Roth EF Jr, Cheng B, Rybicki AC, Sussman II, Wong M, Ranney HM, Nagel RL, Schwartz RS (1990) Growth of plasmodium falciparum in human erythrocytes containing abnormal membrane proteins. Proc Natl Acad Sci USA 87:7339–7343
Speicher DW, Morrow JS, Knowles WJ, Marchesi VT (1982) A structural model of human erythrocyte spectrin. Alignment of chemical and functional domains. J Biol Chem 257:9093–9101
Speicher DW, Davies G, Marchesi VT (1983) Structure of human erythrocyte spectrin. II. The sequence of the α I domain. J Biol Chem 258:14938–14947
Viglietto G, Montanaro V, Calabrò V, Vallone D, D'Urso M, Persico MG, Battistuzzi G (1990) Common glucose-6-phosphate dehydrogenase (G-6-PD) variants from the Italian population: biochemical and molecular characterization. Ann Hum Genet 54:1–15
Vulliamy TJ, D'Urso M, Battistuzzi G, Estrada M, Foulkes NS, Martini G, Calabrò V, Poggi V, Giordano R, Town M, Luzzatto L, Persico MG (1988) Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe haemolytic anemia. Proc Natl Acad Sci USA 85:5171–5175
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miraglia del Giudice, E., Ducluze, M.T., Alloisio, N. et al. αI/65 Hereditary elliptocytosis in Southern Italy: Evidence for an African origin. Hum Genet 89, 553–556 (1992). https://doi.org/10.1007/BF00219183
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00219183