Hereditary spherocytosis associated with deletion of human erythrocyte ankyrin gene on chromosome 8

Samuel E. Lux, William T. Tse, Joan C. Menninger, Kathryn M. John, Peter Harris, Oded Shalev, Robert R. Chilcote, Sally L. Marchesi, Paul C. Watkins, Vann Bennett, Sue McIntosh, Francis S. Collins, Uta Francke, David C. Ward, Bernard G. Forget

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


HEREDITARY spherocytosis (HS) is one of the most common hereditary haemolytic anaemias1. HS red cells from both autosound dominant and recessive variants are spectrin-deficient2,3, which correlates with the severity of the disease3. Some patients with recessive HS have a mutation in the spectrin α-2 domain (S.L.M. et al., unpublished observations), and a few dominant HS patients have an unstable β-spectrin that is easily oxidized4, which damages the protein 4.1 binding site and weakens spectrin-actin interactions5,6. In most patients, however, the cause of spectrin deficiency is unknown. The α- and β-spectrin loci are on chromosomes 1 and 14 respectively7-9. The only other genetic locus for HS is SPH2, on the short arm of chromosome 8 (8p11)10-14. This does not correspond to any of the known loci of genes for red cell membrane proteins including protein 4.1 (Ip36.2-p34)15, the anion exchange protein (AE1, band 3; 17q21-qter)16,17, glycophorin C (2ql4-q21)18, and β-actin (7pter-q22)19. Human erthrocyte ankyrin, which links β-spectrin to the anion exchange protein, has recently been cloned20,21. We now show that the ankyrin gene maps to chromosome 8pll.2, and that one copy is missing from DNA of two unrelated children with severe HS and heterozygous deletions of chromosome 8 (del(8Xpll-p21.1)). Affected red cells are also ankyrin-deficient. The data suggest that defects or deficiency or ankyrin are responsible for HS at the SPH2 locus.

Original languageEnglish (US)
Pages (from-to)736-739
Number of pages4
Issue number6277
StatePublished - 1990

ASJC Scopus subject areas

  • General


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