Novel mutations of the ATP7B gene among 109 Hungarian patients with Wilson's disease.

Background/aims Diagnosis of Wilson's disease may be difficult in patients presenting with liver disease and in asymptomatic siblings. The aim of the present study was to assess the impact of genetic testing for diagnosis of the disease in a large cohort (n = 109) from Hungary. Patients/methods One hundred and nine patients with Wilson's disease were studied (65 men and 44 women; mean age at onset of symptoms: 20 9 years). Diagnosis of the disease was based on typical clinical and laboratory features (all had a Wilson's disease score of >=, 4). H1 069Q was assessed by the semi-nested polymerase chain reaction-based restriction fragment length polymorphism assay. H1 069Q heterozygotes and H1 069Q negative samples were then screened for mutations (on exons 6 to 20) by denaturating high-performance liquid chromatography and than sequenced on a genetic analyser. Results Twenty-three different mutations were found. H1 069Q was the most frequent mutation in Hungary, detected in 77 patients (71%). Fourteen further known mutations were found by sequencing. We identified eight new mis-sense mutations not described before: N6761, S693Y, Y715H, M769L, W939C, P1 273S, G1 281 D and G1 341 V. In 36/109 patients (33%) the diagnosis of Wilson's disease was established by adding mutational analysis. The Kayser-Fleischer ring was more frequent in H1 069Q homozygous patients and their mean age at the time of diagnosis was higher than in patients heterozygous or negative for H1069Q. Conclusion Eight novel mutations in addition to the 15 that are already known were found in Hungarian patients with Wilson's disease. Our results underline the importance and usefulness of genetic testing for patients presenting with liver disease and for family screening.