Abstract: Objective Genetic testing and prenatal diagnosis were used to identify the pathogenic gene variation of Wilson disease in a family. Methods Whole exon sequencing was used to analyze the proband with hepatolenticular degeneration in the family and Sanger sequencing was used to identify the suspected pathogenic variation screened by the proband and his parents. Amniocentesis was performed on the second fetus for prenatal genetic diagnosis. Results It was found that the proband had complex heterozygous variation of ATP7B gene. The missense variation was named NM_000053.3:c.2333G>T(p.Arg778Leu)from his father and the deletion variation was named NM_000053.3:c.208delC(p.Gln70Ser fs*4)from his mother. The missense variation c.2333G>T had been reported and the deletion variation c.208delC had been not reported. The proband's mother underwent prenatal genetic diagnosis at 20 weeks of pregnancy. It was found that the fetus only carried the c.208delC deletion variation from the mother and the c.2333 locus was wild type. The fetus and the proband had different genotypes which predicted that the fetus would not have the same clinical manifestations of hepatolenticular degeneration as the proband. Conclusion The abnormal clinical phenotype of the Wilson disease proband is caused by the complex heterozygous variation of ATP7B gene. It provides the basis for the genetic counseling and prenatal diagnosis for parents who will give birth to a second child.

Key words: Wilson disease, Gene variation, ATP7B gene, Sanger sequencing