Detection of the His1069Gln Mutation in Wilson Disease by Rapid Polymerase Chain Reaction

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Abstract
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. 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. Cross-sectional study. University medical center. 83 patients from 72 families and 98 relatives of 11 homozygous index patients. Results of a semi-nested PCR-based assay to detect the His 1069Gln mutation in Wilson disease, clinical symptoms, and liver histologic findings. 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). 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.

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