Objective: To investigate the correlation between genotype and phenotype of patients with Wilson disease (WD) in the Chinese population.
Methods: Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and subsequent direct sequencing to identify the mutations of ATP7B. Statistical analysis was performed using t test or chi(2) test.
Results: The common mutation Arg778Leu was homozygous in 18 patients. It was also found to be heterozygous in 29 patients. 11 of 29 patients who carried another missense mutation in the other chromosome were regarded as Arg778Leu compound heterozygotes. We observed that the average age at onset in Arg778Leu homozygotes was significantly younger than that in Arg778Leu compound heterozygotes (P < 0.05). The average ceruloplasmin level of Arg778Leu homozygotes was significantly lower than that of Arg778Leu compound heterozygotes (P < 0.001).
Conclusion: The result shows that Arg778Leu homozygotes are associated with the early onset of WD with hepatic presentation. The Arg778Leu mutation is not a mild mutation. It has severe effects on the function of ATP7B.