A novel I247T missense mutation in the haptoglobin 2 beta-chain decreases the expression of the protein and is associated with ahaptoglobinemia.
We have identified a novel base substitution at codon 247 in the beta-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 beta-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 -61C Hp(2)/-61C Hp(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.
Teye
Kwesi
K
Division of Human Genetics, Department of Forensic Medicine, Kurume University School of Medicine, 830-0011 Kurume, Japan.
Quaye
Isaac K E
IK
Koda
Yoshiro
Y
Soejima
Mikiko
M
Pang
Hao
H
Tsuneoka
Makoto
M
Amoah
Albert G B
AG
Adjei
Andrew
A
Kimura
Hiroshi
H
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D005869:Ghana; D006242:Haptoglobins / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D005779:Immunodiffusion; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D006242:Haptoglobins