WD患者ATP7B基因突变热点及其与临床表型相关性分析-内科学专业论文.docxVIP

广东药学院硕士研究生学位论文 广东药学院硕士研究生学位论文 ii ii patients and their clinical phenotypes were analyzed. Results: 53 different melting profile shapes were found in ATP7B gene of 75 WD patients which came from middle and eastern China. It was proved by DNA sequencing, 24 missens mutations, 5 nonsens mutations, 3 splice-site mutations, 6 frameshift mutations and 13 polymorphism were found, including 2 novel polymorphism：Ile613Ile, Trp974Trp, and 10 novel mutations（not found in normal group）: 1875-1876dupAATT, 2120AG(Gln707Arg), 2121+3AT, 2564CA(Ser855Tyr), 2620GC(Ala874Ser), 2761AC(Ser921Arg), 3236GT(Cys1039Phe), 3244-2AC, 3446GA(Gly1149Glu), 3682AT(Arg1228stop). The rate of mutations of 75 WD patients was 90.67%（68/75），and its frequency of gene mutation was 68.67%(103/150). The rate of Arg778Leu mutation was 42.67%(32/75), and its frequency of chromosome mutation was 22.67%(34/150). The rate of Ile1148Thr mutation was 18.67% (14/75), and its frequency of chromosome mutation was 9.3%(14/150). The rate of mutation of exon8, 12 and 16 was 48%（72/150）。 There were no relationships between the mutation types of ATP7B and the levels of CP and SC(P0.05). The level of SC of Arg778Leu heterozygous mutation group was higher than no Arg778Leu mutation group (P=0.012), The level of SC of Arg778Leu homozygous mutation group was higher than no Arg778Leu mutation group (P=0.021); The level of CP of Ile1148Thr heterozygous mutation group was higher than no Ile1148Thr mutation group (P=0.000). There were no relationships between the genotypes of Arg778Leu mutation , Ile1148Thr mutation, mutation types and their clinical phenotypes of clinical types, gender, first symptoms, courses of disease, age of onset (P0.05). Conclusion: DHPLC, which is a quick and easy method, can be used in clinical gene diagnosis. Ile1148Thr mutation is another highly frequent spot of ATP7B mutation in Chinese WD patients. There is a difficult relationship between genotype and phenotype, it is necessary to study fur