title: Novel mutations of the ATP7B gene among 109 Hungarian patients with Wilson's disease.
abstract: OBJECTIVE
  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.
  
  
  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 >or=4). H1069Q was assessed by the semi-nested polymerase chain reaction-based restriction fragment length polymorphism assay. H1069Q heterozygotes and H1069Q 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. H1069Q 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: N676I, S693Y, Y715H, M769L, W939C, P1273S, G1281D and G1341V. 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 H1069Q homozygous patients and their mean age at the time of diagnosis was higher than in patients heterozygous or negative for H1069Q.
  
  
  CONCLUSIONS
  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.
authors.affiliation: First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Aniko
authors.initials: A
authors.lastname: Folhoffer
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Timea
authors.initials: T
authors.lastname: Csak
authors.forename: Andrea
authors.initials: A
authors.lastname: Horvath
authors.forename: Dalma
authors.initials: D
authors.lastname: Hegedus
authors.forename: Gabor
authors.initials: G
authors.lastname: Firneisz
authors.forename: Janos
authors.initials: J
authors.lastname: Osztovits
authors.forename: Janos Pal
authors.initials: JP
authors.lastname: Kosa
authors.forename: Claudia
authors.initials: C
authors.lastname: Willheim-Polli
authors.forename: Laszlo
authors.initials: L
authors.lastname: Szonyi
authors.forename: Margit
authors.initials: M
authors.lastname: Abonyi
authors.forename: Peter Laszlo
authors.initials: PL
authors.lastname: Lakatos
authors.forename: Ferenc
authors.initials: F
authors.lastname: Szalay
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases