Response to mivacurium in a patient compound heterozygous for a novel and a known silent mutation in the butyrylcholinesterase gene - Genotyping by sequencing

Citation
Mr. Gatke et al., Response to mivacurium in a patient compound heterozygous for a novel and a known silent mutation in the butyrylcholinesterase gene - Genotyping by sequencing, ANESTHESIOL, 95(3), 2001, pp. 600-606
Citations number
33
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Journal title
ANESTHESIOLOGY
ISSN journal
00033022 → ACNP
Volume
95
Issue
3
Year of publication
2001
Pages
600 - 606
Database
ISI
SICI code
0003-3022(200109)95:3<600:RTMIAP>2.0.ZU;2-O
Abstract
Background: Patients who are homozygous for the atypical mutation, compound heterozygous for atypical and silent mutations, or homozygous for silent m utations (SS) respond to mivacurium with extensively prolonged neuromuscula r block. Although important, exact phenotyping of these patients is difficu lt. This article presents the pharmacodynamics and pharmacokinetics of a no rmal dose of mivacurium in a patient with phenotype SS, including a pedigre e analysis and delineation of the molecular genetic method used to identify the genotype. Methods: The neuromuscular block following administration of mivacurium, at a dose of 0.14 mg/kg, was monitored in a 30-yr-old healthy man with use of a mechanosensor and mechanomyography, and times to different levels of rec overy were measured. Venous samples for determination of the mivacurium iso mers were collected during the interval 134-494 min after administration of mivacurium, and the terminal half-lives were calculated. Butyrylcholineste rase activity, phenotype, and genotype were determined for both the patient and the family. Complete nucleotide sequencing was used to identify the ge notype. Results: A train-of-four ratio of 0.75 was reached 469 min after the inject ion of mivacurium. The terminal elimination half-lives of the mivacurium is omers, cis-trans and trans-trans, were 90 min. Complete nucleotide sequenci ng revealed two point mutations, the known silent variant S7 and a previous ly undescribed mutation of amino acid residue 170 introducing a stop codon. Conclusions: The patient was compound heterozygous for silent mutations in the butyrylcholinesterase gene. The response to mivacurium was an extensive ly prolonged duration of action. Identification of the rare silent mutation s presupposes access to modern molecular genetic methods such as complete n ucleotide sequencing.