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We have previously identified, in three British families having an index child with frequent infections, a point mutation (GGC-->GAC) in codon 54 of exon 1 of the gene for the human lectin mannose binding protein (MBP). This was associated with low serum levels of this complement activating protein and would be anticipated to impair opsonization of mannose rich microorganisms. We now report a second point mutation (GGA-->GAA) in Gambians from West Africa, involving codon 57 of exon 1. By substituting carboxylic acids for axial glycines in the translated proteins both mutations would be expected to disrupt the secondary structure of the collagenous triple helix of the 96 kDa MBP subunits. In the Gambians the codon 57 mutation was studied by PCR, sequence analysis and restriction analysis and found to be remarkably common (frequency of the mutant gene 0.29 in adults and 0.23 in newborns) whereas the codon 54 mutation was very rare (frequency 0.003). However, the codon 54 mutation was frequent in both a British Caucasian and a Hong Kong Chinese population (frequency of the mutant gene 0.17 and 0.11 respectively). It was predicted that both homozygous and heterozygous individuals would have profoundly reduced serum levels of the protein and this was confirmed by immunoassay as was the reduced capacity of such sera to activate complement through the MBP initiated classical pathway. Our data indicate that the two mutations have arisen independently since the divergence of African and non African populations and both have attained high frequencies.

Original publication

DOI

10.1093/hmg/1.9.709

Type

Journal article

Journal

Hum Mol Genet

Publication Date

12/1992

Volume

1

Pages

709 - 715

Keywords

Adult, African Continental Ancestry Group, Asian Continental Ancestry Group, Base Sequence, Carrier Proteins, Codon, DNA, European Continental Ancestry Group, Exons, Female, Gambia, Gene Frequency, Genotype, Heterozygote, Homozygote, Hong Kong, Humans, Infant, Newborn, Male, Mannose, Mannose-Binding Lectins, Molecular Sequence Data, Oligodeoxyribonucleotides, Phylogeny, Point Mutation, Polymerase Chain Reaction, United Kingdom