Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase - PubMed (original) (raw)

Case Reports

Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase

M C McGuire et al. Proc Natl Acad Sci U S A. 1989 Feb.

Abstract

A point mutation in the gene for human serum cholinesterase was identified that changes Asp-70 to Gly in the atypical form of serum cholinesterase. The mutation in nucleotide 209, which changes codon 70 from GAT to GGT, was found by sequencing a genomic clone and sequencing selected regions of DNA amplified by the polymerase chain reaction. The entire coding sequences for usual and atypical cholinesterases were compared, and no other consistent base differences were found. A polymorphic site near the C terminus of the coded region was detected, but neither allele at this locus segregated consistently with the atypical trait. The nucleotide-209 mutation was detected in all five atypical cholinesterase families examined. There was complete concordance between this mutation and serum cholinesterase phenotypes for all 14 heterozygous and 6 homozygous atypical subjects tested. The mutation causes the loss of a Sau3A1 restriction site; the resulting DNA fragment length polymorphism was verified by electrophoresis of 32P-labeled DNA restriction fragments from usual and atypical subjects. Dot-blot hybridization analysis with a 19-mer allele-specific probe to the DNA amplified by the polymerase chain reaction distinguished between the usual and atypical genotypes. We conclude that the Asp-70----Gly mutation (acidic to neutral amino acid substitution) accounts for reduced affinity of atypical cholinesterase for choline esters and that Asp-70 must be an important component of the anionic site. Heterogeneity in atypical alleles may exist, but the Asp-70 point mutation may represent an appreciable portion of the atypical gene pool.

PubMed Disclaimer

References

    1. J Clin Invest. 1966 Mar;45(3):380-7 - PubMed
    1. Ann Hum Genet. 1959 Jul;23:239-50 - PubMed
    1. Mol Pharmacol. 1968 May;4(3):274-87 - PubMed
    1. Enzyme. 1974;18(5):279-92 - PubMed
    1. J Biol Chem. 1978 Jan 25;253(2):361-6 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources