Background: Wilson disease is an autosomal recessive disorder of copper transport and is characterized by excessive accumulation of cellular copper in the liver and other tissues because of impaired biliary copper excretion and disturbed incorporation of copper into ceruloplasmin. Hepatic failure and neuronal degeneration are the major symptoms of Wilson disease. Mutations in the ATP7B gene are the major cause of Wilson disease.
Case presentation: In this study we have screened one pedigree with several affected members, including a 24-year-old Iranian woman and a 20-year-old Iranian man, who showed psychiatric and neurological symptoms of varying severity, by amplifying the coding regions including exon-intron boundaries with polymerase chain reaction and sequencing. We identified c.1924G>C and c.3809A>G mutations in affected members as compound heterozygote state. These mutations segregated with the disease in the family and they were absent in a cohort of 100 Iranian ethnicity-matched healthy controls.
Conclusions: No homozygote state has been reported for these two variants in public databases. In silico predicting tools consider these two variants to be damaging. So this study introduces the novel combination of c.1924G>C and c.3809A>G variants as a cause for Wilson disease.
Keywords: ATP7B gene; Compound heterozygote; Sequencing; Wilson disease.