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.
Division of Human Genetics, Department of Forensic Medicine, Kurume University School of Medicine, 830-0011 Kurume, Japan.
Kwesi
K
Teye
Isaac K E
IK
Quaye
Yoshiro
Y
Koda
Mikiko
M
Soejima
Hao
H
Pang
Makoto
M
Tsuneoka
Albert G B
AG
Amoah
Andrew
A
Adjei
Hiroshi
H
Kimura
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