High prevalence of fulminant hepatic failure among patients with mutant alleles for truncation of ATP7B in Wilson's disease.
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.
Okada
Toshihide
T
Department of Internal Medicine, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan. okada351116@yahoo.co.jp
Shiono
Yuta
Y
Kaneko
Yoshibumi
Y
Miwa
Kazuhiro
K
Hasatani
Kenkei
K
Hayashi
Yoshiaki
Y
Mibayashi
Hiroshi
H
Aoyagi
Hiroyuki
H
Tsuji
Shigetsugu
S
Yoshimitsu
Masashi
M
Hayashi
Hisao
H
Yamagishi
Masakazu
M
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
D015415:Biomarkers; D027682:Cation Transport Proteins; D018389:Codon, Nonsense; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases