Modulation of clinical expression and band 3 deficiency in hereditary spherocytosis.

Abstract

We present two novel alleles of the anion-exchanger 1 (AE1) gene, allele Coimbra and allele Mondego. Allele Coimbra (V488M, GTG --> ATG) affects a conserved position in the putative second ectoplasmic loop of erythrocyte band 3. In 15 simple heterozygotes, it yielded a mild form of hereditary spherocytosis (HS) with band 3 deficiency (-20% +/- 2%) and a reduced number of 4,4'-diisothiocyano-1,2-diphenylethane-2,2'-disulfonate (H2DIDS) binding sites (-35%). However, two additional heterozygotes presented with an aggravated HS and a more pronounced reduction of band 3 (-40%) and of H2DIDS binding sites (-48%). They carried, in trans to allele Coimbra, allele Mondego, defined by two mutations: E40K, GAG --> AAG, the known mutation Montefiore, and P147S, CCT --> TCT, a novel mutation, both located in the cytoplasmic domain of band 3. Allele Mondego itself resulted in no clinical or hematologic HS signs in the simple heterozygous state. Yet it yielded a slight decrease in band 3 (-6% to -12%) and in the number of H2DIDS binding sites (-19%). Thus, the more pronounced decrease in band 3 in the two compound heterozygotes derived from the additive effects of two unequally expressed AE1 alleles, resulting in a more severe clinical picture.

• Authors: N Alloisio, P Texier, A Vallier, M L Ribeiro, L Morlé, M Bozon, E Bursaux, P Maillet, P Gonçalves, M J Tanner, G Tamagnini, J Delaunay
• Journal: Blood (Blood) Vol. 90 Issue 1 Pg. 414-20 (Jul 01 1997) ISSN: 0006-4971 [Print] United States
• PMID: 9207478 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anion Exchange Protein 1, Erythrocyte

Topics

• Alleles
• Anion Exchange Protein 1, Erythrocyte (deficiency, genetics)
• Female
• Humans
• Male
• Pedigree
• Spherocytosis, Hereditary (genetics)