Study On The Gene Diagnosis And The Genotype-Phenotype Correlation Of Wilson Disease

Objective To determine the hot point mutations of Chinese Wilson disease's gene and explore the methods and importance of gene diagnosis for WD patient. The genotype and phenotype correlation in patients with WD was analyzed.Method Amplified the exon 8, exon 12 and exon 18 of ATP7B gene by polymerase chain reaction. PCR products were analyzed by PCR-SSCP technique and digestion with restriction enzymes. The relativity of the genotype and phenotype of ATP7B gene was investigated.Result 31 WD disease patients from 24 unrelated families and 20 control participates in the study. Gene mutation wasn't found in exon 18 in the 31 patients. Arg778Leu of exon 8 was detected in 35.48%(11/31) patients, 9 patients were heterozygous and 2 patients were homozygous. Thr935Met of exon 12 was detected in 9.68%(3/71)patients, 2 cases were heterozygous and 1 case was homozygous. 45.16% WD disease patients can be detected to identify the two common mutations of ATP7B gene. There was significant difference in the plasma ceruloplasmin levels between the WD patients with Arg778Leu mutations and the others. There was significant correlation between the genotype of Arg778Leu mutation and the phenotype of hepatic damage. The mutation group with Thr935Met wasn't found the close relativity between genotype and phenotype.Conclusion Exon 18 wasn't frequent mutation point in Chinese Wilson disease; Arg778Leu of exon 8 and Thr935Met of exon 12 were hot point mutations of Chinese ATP7B gene; the plasma ceruloplasmin levels of WD patients with Arg778Leu mutations group were significantly different from other patients. The genotype of Arg778Leu mutation correlated to the phenotype of hepatic damage. The mutation group with Thr935Met shows no significant relativity to patient's clinical aspects.