Novel mutation and multiple mutations found in the human butyrylcholinesterase gene

Background: Mutations in human butyrylcholinesterase (BChE) are linked to low BChE activity and abnormal response to muscle relaxants. Methods: Twenty Chinese patients with hepatic disease and low cholinesterase activity, and one Japanese patient and her mother were tested for BChE activity and BChE phenotype. The butyrylcholinesterase (BCHE gene) was amplified by polymerase chain reaction (PCR) and sequenced. Mutant BChE was expressed in 293 cells. Results: A novel mutation was found in one Chinese patient at nucleotide 943, where A was changed to T (943 A→T), causing substitution of threonine 315 by serine (T315S). The T315S mutant had half of the normal BChE activity. One Japanese patient with low BChE activity had three nucleotide substitutions, 355 C→T, 988 T→A, and 1615 G→A. The amino acid substitutions were Q119stop, L330I, and A539T, respectively. The single mutant L330I had low BChE activity, but the double mutant L330I/A539T had normal activity. Conclusions: The L330I and the novel T315S mutation caused a decreased BChE activity. The T315S mutation is one of the first BChE mutations reported in the Chinese population. Multiple mutations in BChE may interact with each other in an intramolecular manner.