a few facts about biology
For anyone out there that is left that is still open to receiving some information, this post is for you.
I think one of the problems that is happening is that people are thinking that "clinical HCM" is the *only* bad thing about HCM and the c-MyBPC3
test.
So...let's define some terms. Clinical HCM means a cat has symptoms
that a general practice vet could detect in the clinic during a vet visit. These symptoms are evident in cats that are very severly affected by
HCM--symptoms like labored breathing, hind limb paralysis, etc. Another clinical symptom that may be present (although there are plenty of cases
where it's not) are heart murmurs. Heart murmurs are a clinical sign, and can indicate mild disease or severe.
Clinical HCM = BAD
Next, there are sub-clinical signs of HCM that can be detected by ultrasound by experienced veterinary cardiologists. Let's call these
echocardiographic signs of HCM. These can include thickened diastolic wall measurements, systolic motion of the mitral valve, end systolic cavity
obliteration, turbulance in the chambers of the left heart, and dynamic outflow tract obstruction. With ultrasound, one can detect earlier stages of
the disease. This is why, for years and years now, every responsible breeder has recognized the value of regular cardiac ultrasound as a screening
tool for breeding cats.
As more and more cats have been ultrasounded periodically and as they
have been followed for older and older ages, it has become apparent that HCM can strike early and progress rapidly and lead to sudden death, or, it
can begin gradually, and only be picked up on ultrasound at an older age (7-10 years old.) As more breeders screen their cats with more
cardiologists, the cardiologists have revised their picture of the true nature of the disease. We see a continuum of symptoms, of age of onset, of
severity, and of final outcome (meaning heart failure, saddle thrombus, or sudden death).
But ultrasound is not a perfect tool. Breeders have long recognized
that a clean ultrasound one year doesn't mean the cat is healthy, it
just means that HCM, if present, may not have progressed far enough
to be detected by *that* detection method. Still, it was all we had, so we all availed ourselves of the latest tools. So, a second conclusion presents
itself:
Echocardiographic evidence of HCM = BAD
Now we have a DNA test. The DNA test tells us if the cat has normal genes or a genetic mutation that has been scientifically shown to cause HCM.
The specific gene is cardiac Myosin Binding Protein C (c-MyBPC3). The job of this gene is to provide the instructions to manufacture the
c-MyBPC molecule, which is incorporated into the cells of the heart muscle. If normal protein is built, all is well.
If abnormal protein is built, the cat, starting from it's very earliest second of life, is on a course towards HCM disease. How fast it progresses, at
what age the first echocardiographic evidence shows up, indeed, what age the first clinical symptoms appear, are all HIGHLY VARIABLE, even
within the SAME FAMILY. At least some of the variability is also due to genetics. It is likely due to many genetic factors that are not well
understood. Some people call them the "enabling gene", others have invented the term "trigger factor." In truth, nobody knows for certain, but it is
more than one gene, it
is much more complex than these overly simplistic models make it out to be.
This abnormal protein initially causes what is known as myocardial fiber disarray. The muscle cells in the heart do not have a nice orderly
arrangement which is necessary for good contraction efficiency, and for good electrical conduction of the heartbeat.
The specific mutation was shown to change the instructions to build
the protein in a specific way. It causes an alinine molecule to be replaced by a proline molecule in the middle of the protein. This results in a
distortion of the way that the protein folds, and the distortion is shown to cause the heart muscle cells to not be able to contract normally, which in
turn causes the cells to become misaligned. This is the HCM the disease process.
We know for certain that a cat with the mutation is producing a defective protein. We know for certain the cat has the potential to develop HCM
disease symptoms (clinical, or echocardiographic) at any time within it life. We know for certain that the cat can pass on the mutation to its
offspring, and we know for certain that the offspring can have a completely different course of disease than its parents.
If it were practical to take a cardiac muscle biopsy of HCM cats, we would find that this characteristic mycardial fiber disarray was present long
before HCM could be detected by cardiac ultrasound, and long before a cat had clinical symptoms.
Myocardial fiber disarray = BAD
We can now, hopefully, see that HCM is really a disease process. There are a continuum of symptoms, starting from the very subtle, and in
practical terms undetectable, myocardial fiber disarray, and progressing through the first echocardiographic equivocal signs, through more advanced
disease that can be seen on ultrasound but not in the clinic, to the full-blow clinical symptoms that is the true horror of HCM.
The genetic mutation causes a defective heart protein to be built, which in turn cases mis-alignment of heart muscle cells, which leads to thickening,
and all the other signs that are detected on ultrasound, which, when they worsen and progress start to cause clinical symptoms, pain and extreme
discomfort to the cat, and ultimately lead to death.
DNA Mutation = BAD
For the purposes of selecting which cats to breed, if you wouldn't breed a cat with severe clinical HCM symptoms, or you wouldn't breed a cat that
is diagnosed with HCM by ultrasound, why on this green earth would anyone argue that it is okay to breed a cat with the genetic mutation that sets
this whole process into motion?
There is no reason to "wait and see", there are no "special lines that need preserving", there are only two choices here, are you part of the problem or
are you part of the solution? Are you going to DNA test your breeding cats and alter the positives, or are you going to ignore the facts and subscribe
to the fantasy?
To breeders and to pet people: Ask to see the DNA test reports for the kitten you are buying, or for the parents of the kitten you are buying. Run
like the wind if anyone minimizes the importance of a positive result. They know not of which they speak.
Cheers,
Paul Huntley
Lunarcoons Maine Coons
San Jose, CA
www.lunarcoons.com