• Open Access

Letter to the Editor

Authors


Dear Editor

In their letter to you, Dr Kittleson and colleagues state their different opinion concerning the interpretation of the results of our study and the value of testing of the A31P mutation in Maine Coon cats. We still believe that our conclusions are correct. Our study was performed because both genetic tests (the A31P and the A74T mutation) are offered by commercial laboratories (at least in Europe) and there were no published studies showing the penetrance of the mutations or their clinical relevance. Some commercial laboratories promote the test heavily and many cats were castrated after they were found to be (heterozygous) positive. Additionally, many cat owners were seeking the advice from cardiologists about the clinical meaning of a positive test. No such data comparing the genotype with the phenotype existed. Although there are “numerous pieces of evidence” that A31P may cause HCM in Maine Coon, as stated by Kittleson and colleagues, there is no published study showing that the A31P mutation causes HCM in a high percentage of field Maine Coon cats. We agree with Kittleson and colleagues stating that our study shows that the penetrance of the A31P is very low and that this is clinically relevant information.

While we apologize for stating incorrectly that Polyphen was used in the study reporting on the A31P polymorphism in Maine Coon cats, Polyphen was used and reported in a different study (using Ragdoll cats) by Meurs et al.1,2 However, we agree (and stated this in our paper) that a software prediction for protein structure does not prove that the mutation is causative. The authors of the letter to the editor state that our selected population was not old enough to make a final conclusion. We agree and stated in our paper that it is desirable to follow up on the cats until they die. Nevertheless, our study included the so far oldest Maine Coon population of any publication and it showed the low penetrance of the A31P mutation. If 85% of the heterozygous positive cats do not have any clinical evidence of HCM or echocardiographic abnormalities at a mean age of 65 months, it is quite unlikely that many of these cats will develop the disease later. In the breeding study by Kittleson, the age of cats (from the unaffected × affected breeding study) at which left ventricular wall thickening or papillary muscle hypertrophy became moderate to severe was between 13 and 48 months (24 ± 13 months).3

TaqMan tests are used by the commercial laboratories in Germany and, therefore, if the tests might not be perfect, then the results provided by these laboratories to breeders are not perfect. Nevertheless, we had sequenced the cats with positive results, as stated in the paper, and got 100% agreement between TaqMan and sequencing. If the test produces false negative cases, they would affect both the healthy and the HCM group, so the effect should equal out.

It is interesting to read that in the research colony of Maine Coon cats every cat homozygous for the A31P mutation has died of severe HCM, most at a young age. We did not argue that the A31P mutation may not be clinically relevant in familial HCM, such as in humans, or in the UC Davis colony. However, even if there is preliminary evidence that “a large percentage of MC cats in the world (including Europe) with the A31P mutation are related to the stud cat that was the founder of the colony at UC Davis,” our results show that although we only had a few cats that were homozygous for the A31P mutation, they can live disease free for many years or may never develop HCM. Again, this shows that there are differences between field cats and cats from the UC Davis colony. We therefore doubt that making breeding decisions based upon a test with such a low penetrance and clinical relevance in field cats is unlikely to improve the health of the Maine Coon breed. We also appreciate that the authors agree at least with the results of our study concerning the A74T mutation, although it was based on the same study design.

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