Z Gastroenterol 2008; 46 - A9
DOI: 10.1055/s-2008-1081516

Identification of a novel mutation in Wilson disease patients from upper-Austria: A genetic and clinical study

H Hofer 1, C Willheim-Polli 1, F Hackl 2, P Knoflach 3, C Gabriel 4, P Ferenci 1
  • 1Internal Medicine III, Dept. of Gastroenterology and Hepatology, Medical University of Vienna
  • 2Department of Internal Medicine, KH Diakonissen, Linz
  • 3Department of Internal Medicine, KH Barmherzigen Brüder, Wels
  • 4Red Cross Blood Transfusion Center, Linz, Austria

Background and Aim: Wilson disease (WD), an autosomal recessive disorder of copper metabolism is caused by mutations in the ATP7B gene, a copper transporting ATPase. More than 200 mutations were reported so far, most of them occurring in single families. In the present study we describe 11 patients with a novel mutation in exon 9 of the ATP7B gene. Ten of them originating from the federal state of Upper-Austria with a population of about 1000000.

Patients and Methods: The ATP7B gene was analyzed for mutations by denaturing HPLC and direct sequencing. DNA from 100 healthy blood donors from the same geographic area was examined as control.

Results: Out of 145 patients with WD originating from Austria 10 patients (3 male, age: 20 [10–30] median [range]) carried a yet undescribed point mutation in exon 9 of ATP7B (R816S). One additional patient carrying the mutation originated from Serbia.

All patients were heterozygous for R816S. Five patients were compound heterozygous for H1090Q/R816S. Three patients had genotype P539L/R816S, one patient G710S/R816S, one patient 2299insC/R816S and one patient was only heterozygous for R816S without further mutations. Interestingly, all but one patient originated within a distinct geographical area in the state of Upper Austria. Six patients presented with hepatic disease, 3 patients with neurologic disease and two patients were asymptomatic sisters of an index case. The remaining patients were unrelated. A liver biopsy was available in 10 patients. Two patients showed advanced liver disease with fulminant hepatic failure and consecutive orthotopic liver transplantation in one. The remaining patients had only mild histological changes, with unspecific histological changes in 3 and chronic hepatitis in 5 patients. Kayser-Fleischer ring was present in 4 patients of whom one patient presented with liver disease. None of the controls investigated carried the mutation.

Conclusion: This novel mutation occurring in a tight geographical area distribution in Austria appears to be associated with a relative mild liver disease, with 80% having no advanced liver fibrosis.