Mutation spectrum and polymorphisms in <i>ATP7B</i> identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease

Wilson's disease (WD), an autosomal recessive copper transport disorder, usually presents with symptoms involving the liver or central nervous system. The disease is caused by a large number of mutations in the ATP7B gene comprising 21 expressed exons. Some of the mutations appear to be population specific, whereas others are found in probands from a variety of different ethnic backgrounds. This paper presents the results of screening of the ATP7B gene by means of the direct sequencing of all exons in the gene in 39 Han and one Hui ethnic Chinese patients. Nineteen novel mutations were revealed along with nine others that have been previously described; 57.5% of the mutations were located in exons 8, 13, and 12. In particular, the Arg778Leu mutation in exon 8 was found in 55% of these Chinese patients in at least one allele. Five patients were homozygotes and 17 patients were heterozygotes for Arg778Leu. The detection rate on direct sequencing of the polymerase chain reaction products of all exons of the ATP7B gene in 40 unrelated patients was 83.8% of alleles. Seventeen polymorphisms were also identified in patients and healthy controls. We first reported the presence of ATP7B mutations in Chinese Hui ethnic patients and summarize our results here along with the previously reported findings. A significant correlation between genotype and phenotype was not found in 37 homozygotes and 52 heterozygotes for Arg778Leu.