Background: Most known mutations in the gene associated with Wilson disease are rare. Only the His 1069Gln mutation is found often in patients of Northern or Eastern European origin.
Objective: To examine the frequency of the His 1069Gln mutation in Austrian patients with Wilson disease and their families by using a new, rapid polymerase chain reaction (PCR) test.
Design: Cross-sectional study.
Setting: University medical 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 His 1069Gln mutation in Wilson disease, clinical symptoms, and liver histologic findings.
Results: 20 patients, including 5 siblings, were homozygous for the His1069Gln mutation. Thirty-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 years]; 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 (73.3%) 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). Four of 98 asymptomatic relatives of 11 homozygous index patients were also homozygotes. Heterozygosity was confirmed in 46 relatives (19 parents, 11 children, and 16 distant relatives).
Conclusion: The His 1069Gln mutation was detected in 61% of Austrian patients with Wilson disease. Polymerase chain reaction may be useful for diagnosis and screening of family members of homozygous index patients, even if first-degree relatives are not available for examination.