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

Abstract

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.