DETECTION OF THE HIS1069GLN MUTATION IN WILSON DISEASE BY RAPID POLYMERASE CHAIN-REACTION

Background: Most known mutations in the gene associated with Wilson di sease are rare. Only the His1069Gln mutation is found often in patient s of Northern or Eastern European origin. Objective: To examine the fr equency of the His1069Gln mutation in Austrian patients with Wilson di sease and their families by using a new, rapid polymerase chain reacti on (PCR) test. Design: Cross-sectional study. Setting: University medi cal center. Patients: 83 patients from 72 families and 98 relatives of 11 homozygous index patients. Measurements: Results of a semi-nested PCR-based assay to detect the His1069Gln mutation in Wilson disease, c linical symptoms, and liver histologic findings. Results: 20 patients, including 5 siblings, were homozygous for the His1069Gln mutation. Th irty-three patients, including 4 siblings, were compound heterozygotes . The mutation was not detected in 30 patients, including 2 siblings. Homozygotes were older at onset of symptoms (mean age, 24 +/- 6 years) than compound heterozygotes (17 +/- 6 years [95% CI, 3.3 to 10.7 year s]; P = 0.0135) and patients with other mutations (18 +/- 8 years [CI, 1.8 to 10.2 years]; P = 0.117). Homozygotes were more often female (7 3.3%) than were compound heterozygotes (48% [CI, 0.94% to 2.46%]) and patients with other mutations (50% [CI, 0.91% to 2.37%]) (P = 0.05). F our of 98 asymptomatic relatives of 11 homozygous index patients were also homozygotes. Heterozygosity was confirmed in 46 relatives (19 par ents, 11 children, and 16 distant relatives). Conclusion: The His1069G ln mutation was detected in 61% of Austrian patients with Wilson disea se. Polymerase chain reaction may be useful for diagnosis and screenin g of family members of homozygous index patients, even if first-degree relatives are not available for examination.