I got a call from the NorthEast Indiana Genetics Clinic this morning, they had results of my genetic testing for Ehlers Danlos ( classical type) back from the testing lab.
I am a certified mutant of ColType V ( although in my excitement, I forgot to ask if it was ColVa or ColVb- they are mailing the report to me, so I will find out soon enough). The coolest part ( ???) is that this is a relatively new mutation. They said the testing lab said they had seen it in one other case, but with no details).
The mutation is in the 3rd exon, with a point mutation that changes an alanine to a valine. Sounds small, right? How could that be significant?
Here is an Alanine molecule:
And here is a Valine molecule:
Note that extra branch on the Valine molecule.
Protein Structure is highly dependent on the interactions ( physical and molecular) between the amino acids that make it up. In a molecule like collagen, which is highly dependent on large numbers of proteins correctly lining up and inter-twining to provide correct strength and function, you can see why having an extra piece of a molecule poking out would disrupt the normal strength and function.
In addition to physical problems, a Valine is almost 3 times more hydrophobic than an alanine, which would disrupt the series of hydrogen bonds which normally hold these molecules in their folded shapes and together with each other.
Alanine is by definition an amino acid that is conducive to alpha helix formation, and valine is notoriously a bad alpha helix maker. Other problems with protein folding have been seen with single alanine to valine mutations.
Single point mutations in other genes which result in a change of alanine to valine are found as problems in other syndromes or genetic disorders as well. Things like inherited neuropathy, Dyskinesia,and even an inherited prion disease. I am sure there are others my quick search did not turn up.
Since we now have an easy marker to look for, we will be getting both of the girls tested as well. Their appointment is set for early June, which means no results until July or so.