title: Two families with Wilson disease in which siblings showed different phenotypes.
abstract: We investigated two families with Wilson disease in which siblings showed different clinical phenotypes and different ages at onset. In Family 1, the second and fourth male children demonstrated onset of the neurological type of Wilson disease at 16 and 28 years of age, respectively, and the first female child developed the hepatic type at 38 years of age. In Family 2, the second male child showed neurological symptoms at 32 years of age and was diagnosed as having the hepatoneurological type of Wilson disease; then the 35-year-old first female child was found to have the hepatic type by familial screening. We performed mutation analysis of the ATP7B gene for these patients, and found that the mutation was a compound heterozygote in both families. Previous reports of siblings with Wilson disease have shown an identical clinical phenotype and similar ages at onset. In addition, hepatic-type cases generally occur at lower ages compared with the neurological type. In the present investigation, however, younger patients showed neurological symptoms earlier than their older siblings, and clinical phenotypes differed among siblings in both families. These cases appear to be rare. Individual differences in copper accumulation in hepatic cells and intolerance to copper toxicity might be the reason for this phenomenon. Furthermore, there might be a difference in the dominance of the allele expressing ATP7B protein among these cases, resulting in different clinical phenotypes, because all patients of both families were found to be compound heterozygotes.
authors.affiliation: Second Department of Pediatrics, Toho University School of Medicine, Ohashi Hospital, 2-17-6 Ohashi, Meguro-ku, Tokyo 153-8515, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Takeshita
authors.forename: Norikazu
authors.initials: N
authors.lastname: Shimizu
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakazono
authors.forename: Miyuki
authors.initials: M
authors.lastname: Saitou
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Fujikawa
authors.forename: Tsugutoshi
authors.initials: T
authors.lastname: Aoki
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases