Maekawa M, Sudo K, Kanno T, Kotani K, Dey D C, Ishikawa J, Izumi M, Etoh K
Department of Laboratory Medicine, Hamamatsu University School of Medicine, Japan.
Clin Chim Acta. 1995 Feb 28;235(1):41-57. doi: 10.1016/0009-8981(95)06014-1.
Three Japanese patients showed very low butyrylcholinesterase activity in their sera and appeared to be homozygous for silent genes for butyrylcholinesterase. From DNA analysis, all three patients were compound heterozygotes: GGA(Gly) to CGA(Arg) at codon 365 (G365R) and TTC(Phe) to TCC(Ser) at codon 418 (F418S) in patient 1, G365R and CGT(Arg) to TGT(Cys) at codon 515 (R515C) in patient 2 and ACT(Thr) to CCT(Pro) at codon 250 (T250P) and AGA(Arg) to TGA(Stop) at codon 465 (R465X) in patient 3. The K-variant, GCA(Ala) to ACA(Thr) at codon 539, was also found in patients 1 and 2. Simple identification methods for all the mutations were developed and applied to family analysis and control individuals. The mutant alleles (with silent gene and K-variant) were segregated as predicted by theory in pedigrees of patients 1 and 2. Four of the mutations, F418S, R515C, T250P and R465X, were initially discovered in Japan and genetic heterogeneity among the human population for the butyrylcholinesterase gene was suggested.
三名日本患者血清中的丁酰胆碱酯酶活性极低，似乎是丁酰胆碱酯酶沉默基因的纯合子。通过DNA分析，所有三名患者均为复合杂合子：患者1中密码子365处的GGA（甘氨酸）突变为CGA（精氨酸）（G365R），密码子418处的TTC（苯丙氨酸）突变为TCC（丝氨酸）（F418S）；患者2中为G365R以及密码子515处的CGT（精氨酸）突变为TGT（半胱氨酸）（R515C）；患者3中为密码子250处的ACT（苏氨酸）突变为CCT（脯氨酸）（T250P）以及密码子465处的AGA（精氨酸）突变为TGA（终止密码子）（R465X）。密码子539处的K变异体，即GCA（丙氨酸）突变为ACA（苏氨酸），也在患者1和患者2中被发现。针对所有这些突变开发了简单的鉴定方法，并应用于家系分析和对照个体。在患者1和患者2的家系中，突变等位基因（包括沉默基因和K变异体）如理论预测的那样进行了分离。其中四个突变，F418S、R515C、T250P和R465X，最初是在日本发现的，这表明人群中丁酰胆碱酯酶基因存在遗传异质性。
