BACKGROUND: Wilson's disease (WD) is an autosomal recessive disorder leading to copper overload, mainly in the liver and brain, due to mutations in the ATP7B gene. About 10% of heterozygous carriers of ATP7B gene mutations have decreased serum ceruloplasmin, posing diagnostic difficulties. CASE REPORT: We report a four-member family wherein the 11-year-old daughter was diagnosed as having WD based on standard biochemical tests and the presence of Kayser Fleischer rings. On screening the entire family for WD, both parents and her eight-year-old brother had no clinical evidence of WD. However, serum ceruloplasmin was markedly decreased in the brother and was borderline low in the father, raising the possibility that the brother also had WD. We used conformation-sensitive gel electrophoresis (CSGE) to screen for mutations in the ATP7B gene in this family. Using CSGE we found that the patient's father and brother had an aberrant pattern in exon 8 of the ATP7B gene, the mother an aberrant pattern in exon 13, while the daughter (the index patient) had aberrant patterns in exons 8 and 13 of the ATP7B gene. DNA sequencing revealed that the index patient was a compound heterozygote with 2292-2312de121bp (a novel mutation) and Arg969Gln mutations, while the father and brother were heterozygous for the 2292-2312de121bp mutation and the mother for the Arg969Gln mutation. CONCLUSIONS: This case report illustrates the utility of CSGE in analyzing mutations in the ATP7B gene to resolve diagnostic dilemmas arising in heterozygous carriers with low serum ceruloplamin.

Keywords: Adenosine Triphosphatases - genetics, Base Sequence, Cation Transport Proteins - genetics, Child, Copper, DNA Mutational Analysis, Electrophoresis, Agar Gel, Family, genetic testing, Hepatolenticular Degeneration - genetics, Molecular Sequence Data, Mutation - genetics, Nucleic Acid Conformation, Polymorphism, Single-Stranded Conformational