However, there was a statement that said, "even though we did not see altered mobility in the proteins, we cannot exclude mutations in the genes."
This statement in our result letter refers to testing for type V collagen alterations in people who have Classical EDS (EDS type I/II). People with EDS type I/II often bruise easily, as do people with some forms of Hypermobile EDS (type III), Kyphoscoliosis EDS (type VI), and EDS type VIII. We are less sure about people with EDS type VII. Some people with an OI/EDS overlap picture have hypermobility in addition to bone fragility and may bruise easily. There are two issues about testing for Vascular EDS (type IV). First, does the testing that we do identify all individuals with the condition? Second, are there mutations in other genes that give rise to the same phenotype or a phenotype sufficiently similar to Vascular EDS (type IV) that it would be considered in the same group.We do not know the answer to the first question. We know that there are some people who have multiple vascular abnormalities, including localized aneurysms, in whom we have not identified abnormalities in type III collagen genes. We know that some of these people may have "familial aneurysm" types of disorders and there are several genes that have been "located" but not identified that could give rise to these clinical pictures. There is an occasional person who the clinician thinks has Vascular EDS (type IV) but in whom we do not find an abnormality. However, many of these come from people who do not have much clinical experience with the disorder so their judgment is has to evaluate. We do know that there are certain classes of mutation in the COL3A1 gene that we find less frequently than we expect. We do not know if individuals with those mutations have an Vascular EDS (type IV) clinical picture or have something else. Is it that our tests miss these people? At this point we don't think so and, instead, think that they may have other, perhaps related, clinical pictures. The reason that we think we find abnormalities in most people is that we not only screen at the protein level but, if there is any question, we screen at the gene level, too. Answered by Peter Byers, MD
This statement "even though we did not see altered mobility in the proteins, we cannot exclude mutations in the genes" is extracted from our "normal" result letter. Because we do diagnostic testing for Vascular EDS (type IV) by examining the protein (type III collagen), it is possible that there are individuals who have COL3A1 gene mutations that we do not detect because the gene mutation is one that doesn't "translate" into a protein abnormality - it doesn't reduce the amount of type III collagen, it doesn't change the size of the molecule, etc. From reviewing clinical histories on patients who have had normal collagen screening studies, we think the likelihood that someone has Vascular EDS (type IV) but we miss it by doing collagen screening is small - 2-3%. In instances where the clinical history is consistent with the Vascular EDS diagnosis, we sometimes do additional COL3A1 gene studies. The decision to do the additional studies is determined by the lab director (Peter Byers) and the patient's doctor after review of their history. Answered by Melanie Pepin MS,CGC