Identification of two different point mutations associated with the fluoride-resistant phenotype for human butyrylcholinesterase.

The fluoride variant of human butyrylcholinesterase owes its name to the observation that it is resistant to inhibition by 0.050 mM sodium fluoride in the in vitro assay. Individuals who are heterozygous for the fluoride and atypical alleles experience about 30 min of apnea, rather than the usual 3-5 min, after receiving succinyldicholine. Earlier the authors reported that the atypical variant has a nucleotide substitution which changes Asp 70 to Gly. In the present work they have identified two different point mutations associated with the fluoride-resistant phentotype. Fluoride-1 has a nucleotide substitution which changes Thr 243 to Met (ACG to ATG). Fluoride-2 has a substitution which changes Gly 390 to Val (GGT to GTT). These results were obtained by DNA sequence analysis of the butyrylcholinesterase gene after amplification by PCR. The subjects for these analyses were 4 patients and 21 family members. 36 refs., 8 figs.