CHARACTERIZATION OF AN UNSTABLE VARIANT (BCHE115D) OF HUMAN BUTYRYLCHOLINESTERASE

An unstable variant of human butyrylcholinesterase (BChE) is described in four apparently unrelated individuals sensitive to succinylcholine . Sequencing of genomic DNA revealed a single nucleotide substitution which results in the replacement of amino acid residue Gly115 by Asp. This variant can be recognized by its increased instability under extr emes of temperature such as heating and also freezing and thawing, bot h in homozygous and heterozygous states. When in heterozygous combinat ion with the Atypical variant, it produces dibucaine and fluoride numb ers which are intermediary between those of Atypical homozygotes and h eterozygotes. After repeated freezing and thawing, however, these valu es approach those of homozygous Atypical plasma. Measurement of activi ty and immunoreactive BChE protein in plasma of individuals representi ng different combinations of this allele indicated that the presence o f the Usual or Atypical enzymes seems to partially protect this varian t from denaturation in vivo. Phenotyping fresh serum or plasma samples , before they are frozen, is critical for the identification of this, and possibly some other, unstable variants.