nemoci-sympt/METABOLISMUS/wilsonova-choroba/priciny

The Wilson's disease gene (ATP7B)

• Chromosome 13 (13q14.3)
• Expressed primarily in the liver, kidney, and placenta
• Gene codes for a P-type (cation transport enzyme) ATPase
• Transports copper into bile
• Incorporates it into ceruloplasmin
• Mutations can be detected in 90% of cases
• 60% are homozygous for ATP7B mutations (two abnormal copies)
• 30% have only one abnormal copy
• 10% have no detectable mutation [3]

• 300 mutations of ATP7B have been described
• Western populations the H1069Q mutation
• Replacement of a histidine by a glutamine at position 1069 in the protein in 37–63% of cases
• China
• R778L (arginine to leucine at 778) is found more often [3]
• H1069Q mutation seems to predict later onset and predominantly neurological problems, according to some studies
• People with only one abnormal gene are carriers (heterozygotes)
• May have mild, but medically insignificant, abnormalities of copper metabolism [3]

Variation in the PRNP gene

• Can modify the course of the disease
• By delaying the age of onset
• Affecting the type of symptoms that develop
• This gene produces prion protein
• Active in the brain and other tissues
• Appears to be involved in transporting copper [3]

Other members of the group not related to ATP7B mutations:

• Indian childhood cirrhosis (ICC)
• Mutations in the KRT8 and the KRT18 gene
• Endemic Tyrolean infantile cirrhosis
• Idiopathic copper toxicosis [3]