Naturally occurring mutation, Asp70his, in human butyrylcholinesterase.
BACKGROUND
People with genetic variants of butyrylcholinesterase can have hours of prolonged apnoea after a normal dose of succinylcholine or mivacurium.


METHODS
Serum samples from 308 persons living in mid-USA were phenotyped to identify the atypical and fluoride variants. 308 samples were analysed for the K variant by DNA amplification, digestion with Mae III and gel electrophoresis. Amplified DNA from 16 samples was sequenced to identify the D70G, T243M and D70H mutations. Values for kcat and Km were determined for the D70H mutant BChE expressed in 293T cells.


RESULTS
A new mutation, Asp70His, was identified. This mutation is located in the peripheral anionic site of butyrylcholinesterase, where it causes a 10-fold decrease in binding affinity for positively charged substrates.


CONCLUSIONS
People homozygous for the Asp70His mutation are expected to have prolonged apnoea in response to succinylcholine or mivacurium, similar to people with the Asp70Gly mutation.
Boeck
Andreea Ticu
AT
University of Nebraska Medical Center, Eppley Institute, Omaha, Nebraska 68198-6805, USA.
Fry
Debra L
DL
Sastre
Antonio
A
Lockridge
Oksana
O
D019943:Amino Acid Substitution / Q000235:genetics; D001049:Apnea / Q000139:chemically induced / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics* / Q000378:metabolism; D044383:Black People / Q000235:genetics; D002091:Butyrylcholinesterase / Q000235:genetics* / Q000378:metabolism; D006639:Histidine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D017354:Point Mutation; D011485:Protein Binding / Q000235:genetics; D013390:Succinylcholine; D044465:White People / Q000235:genetics
D001224:Aspartic Acid; D006639:Histidine; D002091:Butyrylcholinesterase; D013390:Succinylcholine