title: Butyrylcholinesterase (BCHE) genotyping for post-succinylcholine apnea in an Australian population.
abstract: BACKGROUND
  Measurement of plasma butyrylcholinesterase (BChE) activity and inhibitor-based phenotyping are standard methods for identifying patients who experience post-succinylcholine (SC) apnea attributable to inherited variants of the BChE enzyme. Our aim was to develop PCR-based assays for BCHE mutation detection and implement them for routine diagnostic use at a university teaching hospital.
  
  
  METHODS
  Between 1999 and 2002, we genotyped 65 patients referred after prolonged post-SC apnea. Five BCHE gene mutations were analyzed. Competitive oligo-priming (COP)-PCR was used for flu-1, flu-2, and K-variant and direct DNA sequencing analysis for dibucaine and sil-1 mutations. Additional DNA sequencing of BCHE coding regions was provided when the five-mutation screen was negative or mutation findings were inconsistent with enzyme activity.
  
  
  RESULTS
  Genotyping identified 52 patients with primary hypocholinesterasemia attributable to BCHE mutations, and in 44 individuals the abnormalities were detected by the five-mutation screen (detection rate, 85%). Additional sequencing studies revealed mutations in eight other patients, including five with novel mutations. The most common genotype abnormality was compound homozygous dibucaine and homozygous K-variant mutations. No simple homozygotes were found. Of the remaining 13 patients, 3 had normal BChE activity and gene, and 10 were diagnosed with hypocholinesterasemia unrelated to BCHE gene abnormalities.
  
  
  CONCLUSIONS
  A five-mutation screen for investigation of post-SC apnea identified BCHE gene abnormalities for 80% of a referral population. Six new BCHE mutations were identified by sequencing studies of 16 additional patients.
authors.affiliation: Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW 2050, Australia.
authors.forename: Tina
authors.initials: T
authors.lastname: Yen
authors.forename: Brian N
authors.initials: BN
authors.lastname: Nightingale
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Burns
authors.forename: David R
authors.initials: DR
authors.lastname: Sullivan
authors.forename: Peter M
authors.initials: PM
authors.lastname: Stewart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000777:Anesthetics / Q000009:adverse effects*; D001049:Apnea / Q000139:chemically induced / Q000235:genetics*; D001315:Australia; D002091:Butyrylcholinesterase / Q000172:deficiency / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013390:Succinylcholine / Q000009:adverse effects*
chemical_list: D000777:Anesthetics; D002091:Butyrylcholinesterase; D013390:Succinylcholine