Basepaws + Catstradamus: Together in the Fight Against HCM
Hypertrophic cardiomyopathy (HCM) is the most common feline heart disease -- up to 15% of all cats may suffer from it (Payne et al, 2015). This disease affects the cat's myocardium and causes thickening of the heart’s left ventricle. Many cats with HCM can live long and healthy lives, however, for some cats, HCM can be a devastating and lethal disease. Maine Coons and Ragdolls are thought to be at a higher risk from HCM. We have recently lost an office cat to this cruel disease, so we have been extra-focused on adding this marker to our health report.
As we started to introduce this test to our first cohorts of cats, it became evident that this was a MUCH needed test for everyone, particularly our Maine Coons, Maine Coon mixes and other big breeds. One of the first cats that we tested was an internet celebrity of HUGE proportion, the fluffy Samson, aka Catstradamus. Samson is a gorgeous 5-year-old Maine Coon. He’s 4-feet-long, weighs 28lbs and is the largest cat in New York City! Wow! The results of his genetic test, however, took both us and Samson’s family by a surprise.
Samson's HCM test results
The exact cause of HCM in cats can be challenging to identify. So far, the only identified gene related to feline HCM is MYBPC3, a gene that is essential for developing heart muscles. Two different mutations in this gene (A31P and R820W) have been found in Maine Coons (Meurs et al, 2005) and Ragdolls (Meurs et al, 2007), respectively. Cat carrying homozygotes (two copies) of the mutated genes have up to 18-times higher risk of developing complicated cases of HCM.
After the initial test, followed by a confirmatory secondary test, we found that Catstradamus is heterozygous positive for the A31P mutation for HCM. This means that Samson's genome has one copy of the A31P mutation associated with HCM and one copy of the healthy MYBPC3 gene. He is, therefore, 1.8 times more likely to develop HCM than a cat without the mutation. It is important to remember, however, that there are many factors which impact the likelihood of HCM development aside from genetics. Genetic mutations do play a significant role in the development of the disease, but they only represent the risk factor and do NOT guarantee the diagnosis. Therefore, Sampson was NOT diagnosed with HCM, but was found to be at a higher risk for it than other cats.
Samson is the first kitty in our database to test positive for this mutation. We hope to roll this test out to all our pet parents in the coming months though. As terrifying as this information is, it also brings us a tremendous amount of hope. We are happy to be able to warn Samson's fur-dad about his kitty's genetic risk, because we believe that this allows Samson's veterinarian to keep an eye out for any potential symptoms, in order to catch the disease as early as possible and implement the right treatment plan. This can significantly improve overall disease management and increase the quality of Samson's life in case he actually does develop HCM.
How was the test performed?
There are a couple of different methods that can be used to test whether a cat like Catstradamus has one or two copies of the mutation associated with HCM. Some genetic tests use SNP arrays to look for genetic mutations at known locations in the genome. However, heterozygous mutations (one out of two possible copies of the gene are mutated) can be difficult to interpret with this method. Thus, a better option to test for these mutations is through Sanger sequencing method. In this method, many copies of the potential mutation are made generated and then sequenced, producing a chromotogram (see below).
Below is presented Catstradamus's chromatogram which shows that he is a heterozygote (C/G) at the mutational position on the genome (highlighted in red). The chromatogram shows a colored peak for each of the possible genetic bases (A,T,C,G). At the position highlighted in red, we see a peak for a possible G (in black) and also a peak for a possible C (in blue).
At Basepaws, we are developing a similar sequencing-based approach to observe the potential mutations. We sequence the region of the mutation many times and observe the frequency of the mutation. This frequency allows us to assess how likely the mutation exists. For Catstradamus, we sequenced the region of the mutation 23 times. 11 of those 23 showed a 'C' and 12 showed a 'G' allowing us to conclude that he is a carrier of a heterozygous mutation.
What does this information mean for Samson and Jonathan?
Samson is a carrier of only one copy of the mutation associated with a higher risk for HCM. This increases his genetic risk just two times, but in our opinion, this is more than enough to become vigilant. With this information, Samson's guardian is given a unique opportunity to be aware of the risk, and therefore be able to identify any early signs of potential symptoms. Early diagnosis of a disease as cruel as HCM is essential for disease management. Samson's fur-dad Jonathan is making sure to monitor Samson's heart regularly, take him for annual check ups and the kitty's heart is currently purrfectly healthy.
Why is it important to talk about this?
HCM is a devastating disease affecting a terrifying number of cats. It is the #1 cause of death for indoor cats! We strive to raise awareness about HCM via a novel way of genetic risk detection. We hope to draw the attention of as many cat parents as possible to this disease, and therefore aid in the early detection of HCM symptoms. Currently, HCM cats are diagnosed via medical history, physical examination and echocardiogram results. The problem is that this diagnosis is often achieved when the cat is already experiencing serious symptoms of the disease. Once diagnosed, HCM symptoms can be managed but not cured, which is why early detection tremendously aids symptom management and in slowing down the disease progression. Being aware of the genetic risk offers a brand new way of intervention. In light of this, we are taking the opportunity of being featured on ABC’s Shark Tank on April 28th to spread the word and raise awareness about feline HCM.
We want to be able to detect genetic mutations for HCM and other genetic diseases for all Basepaws cats in order to provide cat parents with noteworthy information about the genetic risks lurking in their cats' genes. This information is highly valuable and offers cat owners an opportunity to personalize their cat's healthcare in a way that wasn’t possible before. This is where Basepaws is heading - join us as we work to eradicate preventable genetic diseases in cats everywhere. Special thanks to Jonathan and Catstradamus for joining their forces with us and helping us raise awareness and drive the study of feline genetics.
1. Meurs K, Sanchez X, David RM, Bowles NE, Towbin JA, Reiser PJ, Kittleson JA, Munro MJ, Dryburgh K, MacDonald KA, Kittleson MD. (2005). A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy. Human Molecular Genetics. 14(23). doi:10.1093/hmg/ddi386.
2. Meurs, K, Norgard MM, Ederer MM, Hendrix KP, Kittleson MD. (2007). A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy. Genomics. 90:261-264