PXE Phenodex

PXE Phenodex

SEPTEMBER 15, 2007
By Emilie Lamb, Research Assistant, PXE International
With Sharon Terry, Executive Director, PXE International

The original paper was published in the Journal of Medical Genetics, October 2007, pages 621-628.
This summary first appeared in the Fall 2007 PXE MemberGram.

PDF: Study on the Relationship between Genetic Mutations and Physical Symptoms of PXE
Free article in PubMed




S0no sign


S2plaques of coalesced papules

S3lax and redundant skin



E0no sign

E1peau d'orange

E2angioid streaks

E3bleeding and/or scarring



G0no sign

G1GI bleeding must be diagnosed as related to PXE



V0no sign

V1weak or absent pulses

V2intermittent claudication

V3vascular surgery



C0no sign

C1chest pain/angina/abnormal EKG or abnormal stress test with no symptoms

C2heart attack

Recently, a study was conducted to understand the relationship between the genotype (mutations or changes in the ABCC6 gene) found in individuals with PXE and their phenotype (signs and symptoms). The lead researchers were Drs. Lionel Bercovitch, Jouni Uitto, Anne De Paepe, Denis Viljoen, Ellen Pfendner, Olivier Vanakker, and lay co-investigators Patrick Terry and Sharon Terry. Others who worked on the project and co-wrote the study were: Paul Coucke, Sara Fratta, Susan Hariri, Patricia McAndrew, Monica McClain, Anna-Susan Marais, Michele Ramsay, and Sophia Vourthis.

PXE is caused by changes, or mutations, in the ABCC6 gene that makes a protein involved in moving chemicals in and out of cells. The aim of this study was to identify the genotype (mutations in theABCC6 gene) present in individuals with PXE and to determine if there is a relationship between the mutations and the phenotype. By identifying mutations that are common to PXE, early detection of the disease is easier. Understanding the relationship between the genotype and the phenotype might also allow healthcare providers to predict the severity of the disease.

The study used DNA from 270 individuals who had donated blood to the PXE International BioBank. These individuals were from North America, Europe, Australia, and South Africa.  In addition, to donating blood for genetic studies, the participants answered questions about their family history and signs and symptoms of PXE. Overall, this study found 82 mutations, 39 of these had never been discovered before.

After all of this data was collected, the scientists tried to figure out how the mutation in the gene changed the protein. Some mutations make the protein stop working completely, meaning it can’t transport some substance out of the cell (the substance, called a substrate, is unknown). Other mutations damage the protein, but it still workssomewhat. Some mutations have an unknown effect. After the scientists grouped the individuals based on how their protein was changed, they compared the phenotypes of the groups.

The phenotypes were coded according to the organs affected. To make this as simple as possible, an index was developed, called a Phenodex™ (see the Phenodex™ box). Creating the Phenodex™allowed the phenotype to be reduced to a few numbers. This made it easier to compare it to the genotype.

When these groups were compared, the scientists found no relationship between what mutations they had and their symptoms. This means that they could not look at one person who had mutation A and know that they would have symptom B, or to what degree they would have that symptom. It is not common to be able to predict the future course of adisease like PXE because the genotype is only part of the story – environment (lifestyle, diet, exercise…) accounts for a great deal in the course of a disease. We continue to study PXE, looking at the effects of both genetics and environment.


Defining the Terms

ABCC6 Gene: A piece of DNA that contains instructions, like a recipe, to tell the cell how to make a protein - in this case the gene associated with PXE.

Mutation: A mutation is a change in a gene that can alter the instructions the gene gives the cell.

Proteins: Proteins are molecules in cells that do all of the work, such as transporting substances into or out of the cell.

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