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Thursday, September 27, 2007

Polycystic Liver Disease

Polycystic liver disease (PLD) is associated with the formation of multiple cysts of various sizes in the liver. Sometimes it causes enlargement of the liver and abdominal pain but in most cases there are no symptoms and the patient may be unaware of any problem.

This disease is not the same as the often fatal polycystic kidney disease (PKD) [OMIM 173910] although patients suffering from kidney failure due to PKD will often have cysts in their liver as well.

PLD is inherited as an autosomal dominant trait, which means that you will have liver cysts even if you only inherit one mutant allele from one parent. There are probably several different genes that can be affected but two genes have been identified and characterized [OMIM 174050]. One of them is the SEC63 gene on chromosome 6q21 [OMIM 60648][Entrez Gene 11231]. This gene encodes one of the components of the ER membrane translocon. This is the pore through which newly synthesized is threaded following attachment of the ribosome/signal-recognition-particle complex [Signal Hypothesis] [Human Genes Involved in the Signal Hypothesis Pathway]. The defect in SEC63 probably interferes with sorting and secretion of proteins in the liver and this is what causes the cysts.

The Online Medelian Inheritance in Man (OMIM) database at Johns Hopkins University is one of the best databases in the world.
The known alleles are null mutations meaning that they disrupt synthesis of the protein. It appears that the presence of one defective copy of the SEC63 gene has no effect on normal development or secretion in most tissues but does have a non-lethal effect in liver cells.

The other gene that's associated with polycystic liver disease is PRKCSH, a gene that encodes the β subunit of glucosidase II [OMIM 177060]. This protein plays a role in the glycolsylation of proteins in the endoplasmic reticulum [glycosylation]. Since glysosylation is requried for protein sorting and secretion, it is likely that interference in that process is resposible for liver cycsts. This is the same process that's defective in SEC63 mutants.

[Photo Credit: OSF Heathcare]

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