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首页> 外文期刊>Pharmacogenetics and genomics >Two novel mutations in the BCHE gene in patients with prolonged duration of action of mivacurium or succinylcholine during anaesthesia.
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Two novel mutations in the BCHE gene in patients with prolonged duration of action of mivacurium or succinylcholine during anaesthesia.

机译：麻醉期间米伐库铵或琥珀酰胆碱作用时间延长的患者，BCHE基因中的两个新突变。

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摘要

BACKGROUND: Butyrylcholinesterase (BChE) hydrolyses the neuromuscular blocking agents, succinylcholine and mivacurium used during general anaesthesia. Hereditary low BChE activity may result in an extensively prolonged duration of action of these drugs, especially in patients who are homozygous for the atypical or silent variants. We present three novel mutations in the butyrylcholinesterase gene (BCHE) identified in three families in which a member had experienced severely prolonged duration of action of succinylcholine. METHODS: As the phenotypes of the three probands could not be established with certainty using conventional biochemical tests, DNA samples were collected from two of the probands and four relatives. Genotypes were determined using complete nucleotide sequencing. RESULTS: Three novel mutations were identified: BCHE*FS126, BCHE*I3E4-14C and BCHE*328D. The proband in family 1 was genotyped as BCHE*115D*I3E4-14C/BCHE*FS126, whereas the proband in family 3 was compound heterozygous for BCHE*328D and BCHE*142M. In both patients, BChE activity was below detection limit, and they experienced an extensively prolonged duration of action of succinylcholine. The proband in family 2 was not sequenced, but a relative was heterozygous for BCHE*FS126. BCHE*I3E4-14C was in linkage with a known silent variant. CONCLUSIONS: Two novel variants of BCHE are silencing the enzyme function. BCHE*FS126 results in a truncated protein lacking the active site and is therefore inactive. The second variant is BCHE*328D, also resulting in an inactive protein, as this change in amino acid is radical and furthermore situated in the gorge harbouring the active site. These variants result in extensively prolonged duration of action of succinylcholine.
机译：背景：丁酰胆碱酯酶（BChE）水解全身麻醉期间使用的神经肌肉阻滞剂，琥珀酰胆碱和米维库铵。遗传性的低BChE活性可能导致这些药物的作用时间大大延长，特别是对于非典型或沉默变异体纯合的患者。我们介绍了丁酰胆碱酯酶基因（BCHE）中的三个新突变，其中三个成员的成员经历了琥珀酰胆碱的作用时间严重延长。方法：由于无法通过常规生化试验确定三个先证者的表型，因此从其中两个先证者和四个亲戚中收集了DNA样本。使用完整的核苷酸测序确定基因型。结果：鉴定出三个新的突变：BCHE * FS126，BCHE * I3E4-14C和BCHE * 328D。家族1的先证者的基因型为BCHE * 115D * I3E4-14C / BCHE * FS126，而家族3的先证者为BCHE * 328D和BCHE * 142M的复合杂合子。在这两名患者中，BChE活性均低于检测极限，并且他们经历了琥珀酰胆碱的作用时间大大延长。家族2中的先证者未测序，但亲戚对BCHE * FS126是杂合的。 BCHE * I3E4-14C与已知的沉默变异体有关联。结论：BCHE的两个新变体正在沉默酶的功能。 BCHE * FS126导致截短的蛋白质缺少活性位点，因此是无活性的。第二个变体是BCHE * 328D，它也导致蛋白质失活，因为氨基酸的这种变化是自由基的，而且位于具有活性位点的峡谷中。这些变体导致琥珀酰胆碱的作用时间大大延长。

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