苯丙酮尿症苯丙氨酸羟化酶基因突变检测研究-妇产科学专业论文.docxVIP

广州医学院硕士学位论文苯丙酮尿症苯丙氨酸羟化酶基因突变检测研究 广州医学院硕士学位论文 苯丙酮尿症苯丙氨酸羟化酶基因突变检测研究 PAGE PAGE 4 For family 15 and 16, prenatal diagnosis were performed by HRM and then confirmed by DNA sequencing. Results In this study, a total of twenty-nine different mutations were identified, including fifteen missense mutations, four nonsense mutations, threee splice mutations, two deletion mutations, three silent mutations, one single nucleotide polymorphism, and one frame-shift mutation (c.188_196delCCCACATTG/c.197?insA). In addition, c.188_196delCCCACATTG/c.197?insA,I94V, Q160X, H264R, G312V, and E305K are novel mutations. In the twenty-one patients, two pathogenic mutations were identified in each of the nineteen patients, three pathogenic mutations were identified in the remaining two patients. The fetus from family 15 was diagnosed as normal, the other fetus from family16 was diagnosed as a carrier. By comparing with DNA sequencing, there were neither false positive nor false negative results for HRM analysis.Therefore, in this stud y the sensitivity and specificity for mutation detection by HRM were both 100%. Conclusion This study suggested that HRM is a simple, accurate, rapid, high-throughput and cost-effective genetic analysis approach. It could be applied to mutation scanning of PAH gene, and especially useful for rapid prenatal diagnosis of classical PKU in parents with known mutations. This study enriched the mutation spectrum of PAH gene in the Chinese population. 【Key words 】phenylketonuria(PKU); phenylalanine hydroxylase gene (PAH); high resolution melting (HRM) 缩略词表 英文缩写 PKU PAH 英文全名 phenylketonuria phenylalanine hydroxylase 中文译名 苯丙酮尿症 苯丙氨酸羟化酶 HRM BH4 PTPS DHPR high resolution melting tetrahydrobiopterin 6-pyruvoyl-tetrahydropterin synthase dihydropteridine reductase 高分辨熔解曲线分析 四氢生物蝶呤 6-丙酮酰四氢蝶呤合成酶 二氢生物蝶呤还原酶 GTPCH PCD PCR RFLP STR GTP cyclohydrolase pterin-4a-carbinolamine dehydratase polymerase chain reaction restriction fragment length polymorphism short tandem re