title: High prevalence of fulminant hepatic failure among patients with mutant alleles for truncation of ATP7B in Wilson's disease.
abstract: OBJECTIVE
  Although many mutations of the Wilson's disease (WD) gene (ATP7B) have been reported, few data exist regarding the occurrence of fulminant hepatic failure (FHF). We sought to determine if genotypic assignment according to type of protein-product could be related to the prevalence of FHF among patients with WD.
  
  
  METHODS
  We performed gene analysis in Japanese patients with WD as well as genotype-phenotype analysis in 51 patients. We divided genotypes into two groups according to type of ATP7B product: truncated group [T] consisted of two truncated alleles including nonsense, insertion, deletion, or splice site mutation, and missense group [M] consisted of one or two missense alleles. We also divided phenotypes into two groups: [FHF] group and [non-FHF] group.
  
  
  RESULTS
  We were able to determine genotype in 42 patients. Genotypically, 11 patients were assigned to [T] group and 31 to [M] group. Phenotypically, 4 patients were [FHF] and 38 were [non-FHF]. All patients in [FHF] group belonged to [T] group. The prevalence of [FHF] in [T] group was 36.4% and was significantly higher than in [M] group (p < 0.003).
  
  
  CONCLUSIONS
  These results demonstrated that genotypes for truncation of ATP7B are associated with high prevalence of FHF.
authors.affiliation: Department of Internal Medicine, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan. okada351116@yahoo.co.jp
authors.forename: Toshihide
authors.initials: T
authors.lastname: Okada
authors.forename: Yuta
authors.initials: Y
authors.lastname: Shiono
authors.forename: Yoshibumi
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Miwa
authors.forename: Kenkei
authors.initials: K
authors.lastname: Hasatani
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mibayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aoyagi
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Tsuji
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoshimitsu
authors.forename: Hisao
authors.initials: H
authors.lastname: Hayashi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000483:Alleles; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense; D000073840:Copper-Transporting ATPases; D005260:Female; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D017114:Liver Failure, Acute / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D016254:Mutagenesis, Insertional; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence; D017384:Sequence Deletion
chemical_list: D015415:Biomarkers; D027682:Cation Transport Proteins; D018389:Codon, Nonsense; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases