Genetics FAQ


Frequently Asked Questions - Genetics


  1. Are there any other genes, besides the ABCC6 gene, which are involved in the disease of PXE?
  2. What goes wrong in the ABCC6 gene to cause PXE?
  3. Can researchers manufacture healthy ABCC6 protein and inject it into the body via the bloodstream? 
     

1. Are there any other genes, besides the ABCC6 gene, which are involved in the disease of PXE?


It has been confirmed that pseudoxanthoma elasticum [PXE] is caused by mutations in the ABCC6 gene.  It is also true that most diseases are influenced by more than one gene.

For example, new studies have shown that certain minor changes, called polymorphisms, in the VEGFA gene, which controls the production of the VEGFA protein, can be associated with the development of age-related macular degeneration (AMD).  With this new understanding of the mechanisms behind AMD, researchers in Germany examined how polymorphisms in the VEGFA gene might work in combination with the ABCC6 gene to result in more severe retinal changes and vision loss.  For more information about this study, click here to read a lay summary.  [December 2009]

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2. What goes wrong in the ABCC6 gene to cause PXE?


In a healthy individual, the ABCC6 gene produces the ABCC6 protein, which is a membrane transport protein in various cells, seemingly expressed in abundance in the liver and kidneys.  The ABCC6 protein is called a cell membrane transport protein because it acts like a doorway or a shuttle allowing something, referred to as a substrate, to pass in and out of the cell.

In an autosomal recessive genetic disease like PXE, the ABCC6 gene contains disease-causing mutations in both copies in the individual (everyone has two copies of each gene, in an autosomal dominant disease only one copy has to have a mutation to cause the disease).  The ABCC6 protein it produces is thus abnormal, inactive or nonexistent, and so does not perform its transport function properly.  In the case of PXE, the miscoded ABCC6 protein is not allowing a currently unknown substrate to pass out of cells.  [December 2009]

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3. Can researchers manufacture healthy ABCC6 protein and inject it into the body via the bloodstream?


No, they cannot.  The ABCC6 protein is not free floating in the blood.  Instead it is imbedded in the wall of cells throughout the body, primarily the liver and kidney.  The cells have to be able to make the protein or the body (or a treatment) has to find some way to perform the miscoded protein's function, that is, pump the unknown substrate out of the cell.  Because mouse research has suggested that the unknown substrate circulates in the bloodstream and may have some effect on PXE symptoms, research has been focused on attempting to determine exactly what that substrate is and whether it could be used as a treatment.  [December 2009]

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Disclaimer


These are replies to general and specific questions which have been submitted to us in the past. Our responses may not apply to any particular individual´s situation and are not a substitute for medical advice given by a physician who is familiar with the individual´s case and who has examined the patient. In addition, the responses are updated on a periodic basis but may not be current.