title: Is Wilson's disease caused by a controller gene mutation resulting in perpetuation of the fetal mode of copper metabolism into childhood?
abstract: Wilson's disease is an inborn error of copper metabolism, characterised by raised liver-copper concentrations and low serum levels of copper and caeruloplasmin. The autosomal recessive mode of inheritance strongly suggests that mutation of a single gene causes the impairment of both caeruloplasmin synthesis and biliary copper excretion. The normal infant is born with the biochemical features of Wilson's disease (very high liver-copper levels and low serum copper and caeruloplasmin). Induction of normal copper metabolism after birth results in a fall in liver-copper concentrations and rise in serum caeruloplasmin. The repression of normal copper metabolism in the fetus and its induction after birth is probably regulated by a controller gene. It is suggested that mutation of a controller rather than a structural gene underlies the pathogenesis of Wilson's disease and that the disease results from failure to switch from the positive copper balance of the fetus to the normal copper balance of the child.
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D005809:Genes, Regulator; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008954:Models, Biological; D009154:Mutation; D011247:Pregnancy
chemical_list: D002352:Carrier Proteins; D003300:Copper