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A novel I247T missense mutation in the haptoglobin 2 β-chain decreases the expression of the protein and is associated with ahaptoglobinemia

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We have identified a novel base substitution at codon 247 in the β-chain of the haptoglobin 2 (Hp 2) allele in a Ghanaian with the Hp0 (ahaptoglobinemic) phenotype. The heterozygous T→C substitution caused reduced expression of the protein when the mutant was transfected into COS7 cells. The base substitution resulted in a missense change of the non-polar amino acid isoleucine to the polar amino acid threonine at a position in the β-chain that is highly conserved among several species. We had previously identified a mutation in the Hp gene promoter region for the same individual, which gives her genotype as –61CHp 2/–61CHp 2(I247T). Since the –61C mutation also leads to low Hp expression, the genotype represents the first and most definitive ahaptoglobinemic case reported in Africa.

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This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, the Novartis Foundation (Japan), and the Mitsui Life Social Welfare Foundation.

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Correspondence to Hiroshi Kimura.

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Teye, K., Quaye, I.K.E., Koda, Y. et al. A novel I247T missense mutation in the haptoglobin 2 β-chain decreases the expression of the protein and is associated with ahaptoglobinemia. Hum Genet 114, 499–502 (2004). https://doi.org/10.1007/s00439-004-1098-6

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  • Malaria
  • COS7 Cell
  • Trypanosoma Brucei
  • Gene Promoter Polymorphism
  • Medical School Ethical