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目的确定ankyrin-B基因突变在日本人群QT间期延长综合征中的发病率以及ankyrin-B基因突变与QT间期延长综合征之间的关系。方法我们对相互之间无血缘关系的日本人群已确诊的QT间期延长综合征患者78例(男28例,女50例)进行了研究。在征得患者的同意之后,从其白细胞中提取纯化基因组DNA并行多聚酶链式反应(PCR)扩增。随即对扩增的DNA行单链构像多态性(SSCP)分析。而后将突变或异常的SSCP产物分离后,采用自动荧光测序仪检测DNA序列。最后再用150例正常健康人的DNA作为对照,对上述经测序确认的误义点突变进行PCR-限制性片段长度多态性分析,以进一步证实误义点突变的真实性和可靠性。结果我们在一例确诊的QT间期延长综合征患者的ankyrin-B基因的4603碱基位点上发现了从T到A的突变(T4603A)。出现于基因的第40号外显子上的该误义点突变,导致了氨基酸序列第1535位点上的色氨酸残基被精氨酸残基所取代(W1535R)。而该氨基酸序列正位于ankyrin-B基因高度保守的调节区域。结论新发现的位于ankyrin-B基因调节区域的误义点突变可能是导致4型QT间期延长综合征的原因之一,而该突变似乎并不是导致日本人群4型QT间期延长综合征的主要病因。
Objective To determine the incidence of ankyrin-B gene mutation in the Japanese population with QT prolongation syndrome and the relationship between ankyrin-B gene mutation and QT prolongation syndrome. Methods We studied 78 patients (28 males and 50 females) with confirmed QT prolongation syndrome in unrelated Japanese populations. After consenting patients, purified genomic DNA is extracted from its white blood cells and subjected to polymerase chain reaction (PCR) amplification. The amplified DNA was then subjected to single strand conformational polymorphism (SSCP) analysis. After the mutation or abnormal SSCP product was separated, the DNA sequence was detected by an autofluorescence sequencer. Finally, DNA from 150 normal healthy people was used as a control to analyze the PCR-restriction fragment length polymorphism (PCR-RFLP) analysis on the above-identified sequencing confirmed point mutations to further confirm the authenticity and reliability of the missense point mutation. Results We found a mutation from T to A (T4603A) at the 4603 base site of the ankyrin-B gene in a patient with confirmed QT prolongation syndrome. This missense point mutation that occurs on exon 40 of the gene results in the substitution of the tryptophan residue at position 1535 of the amino acid sequence with an arginine residue (W1535R). This amino acid sequence is located in the highly conserved regulatory region of the ankyrin-B gene. Conclusion The newly discovered missense point mutation in the regulatory region of ankyrin-B may be one of the reasons leading to the type 4 QT prolongation syndrome that does not seem to result from the Japanese population with type 4 QT prolongation syndrome The main cause.