title: ATP7B Gene Mutations in Croatian Patients with Wilson Disease.
abstract: OBJECTIVE
  Wilson disease (WD) is an autosomal recessive disorder of copper metabolism, characterized by its accumulation in tissues which results in hepatic, neurological, and/or psychiatric symptoms. The aim of this study was to investigate the genetics of WD in Croatian patients.
  
  
  METHODS
  Correlation of the clinical presentation subtype and the age at onset of the diagnosis of WD with the ATP7B genotype was investigated in a group of Croatian WD patients. DNA from peripheral blood samples was tested for the p.His1069Gln by direct mutational analysis and other polymorphisms were identified by sequence analysis of coding and flanking intronic regions of ATP7B gene.
  
  
  RESULTS
  In the group of 75 WD patients of Croatian origin, 18 different mutations in ATP7B gene were detected, three of which were novel. The p.His1069Gln mutation was most frequent, being detected in 44 Croatian WD patients (58.7%). Most ATP7B mutations (90.4%) were located in exons 5, 8, 13, 14, and 15.
  
  
  CONCLUSIONS
  Clinical diagnosis of WD was confirmed in 59 patients by detecting mutations on both ATP7B alleles. The age at onset of WD and the type of WD clinical presentation showed no significant correlation with the ATP7B genotype.
authors.affiliation: 1 Department of Laboratory Diagnostics, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Hana
authors.initials: H
authors.lastname: Ljubić
authors.affiliation: 2 Department of Internal Medicine, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Mirjana
authors.initials: M
authors.lastname: Kalauz
authors.affiliation: 3 Department of Neurology, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Srđana
authors.initials: S
authors.lastname: Telarović
authors.affiliation: 4 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna , Vienna, Austria .
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: 2 Department of Internal Medicine, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Rajko
authors.initials: R
authors.lastname: Ostojić
authors.affiliation: 5 Department of Public Health and Clinical and Molecular Medicine, University of Cagliari , Cagliari, Italy .
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Noli
authors.affiliation: 5 Department of Public Health and Clinical and Molecular Medicine, University of Cagliari , Cagliari, Italy .
authors.forename: Maria Barbara
authors.initials: MB
authors.lastname: Lepori
authors.affiliation: 6 Department of Internal Medicine, General Hospital Pula , Pula, Croatia .
authors.forename: Irena
authors.initials: I
authors.lastname: Hrstić
authors.affiliation: 7 Department of Pediatrics, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Jurica
authors.initials: J
authors.lastname: Vuković
authors.affiliation: 2 Department of Internal Medicine, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Marina
authors.initials: M
authors.lastname: Premužić
authors.affiliation: 2 Department of Internal Medicine, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Davor
authors.initials: D
authors.lastname: Radić
authors.affiliation: 2 Department of Internal Medicine, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Katja Grubelić
authors.initials: KG
authors.lastname: Ravić
authors.affiliation: 1 Department of Laboratory Diagnostics, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Jadranka
authors.initials: J
authors.lastname: Sertić
authors.affiliation: 1 Department of Laboratory Diagnostics, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Ana
authors.initials: A
authors.lastname: Merkler
authors.affiliation: 1 Department of Laboratory Diagnostics, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Ana Acman
authors.initials: AA
authors.lastname: Barišić
authors.affiliation: 8 Ospedale Regionale Microcitemie , ASL 8, Cagliari, Italy .
authors.forename: Georgios
authors.initials: G
authors.lastname: Loudianos
authors.affiliation: 2 Department of Internal Medicine, University Hospital Centre Zagreb , Zagreb, Croatia .
authors.forename: Boris
authors.initials: B
authors.lastname: Vucelić
mesh_terms: D000251:Adenosine Triphosphatases / Q000097:blood / Q000235:genetics*; D000328:Adult; D000483:Alleles; D027682:Cation Transport Proteins / Q000097:blood / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D017523:Croatia; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D006527:Hepatolenticular Degeneration / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases