Page 405 - Feline Cardiology

Chapter 28: Cardiac Screening Programs 427

or affected. This is an adult onset disease and the age of change from a guanine to a cytosine in the 31st codon
onset may vary significantly from cat to cat, even within of the gene. This mutation changes the highly conserved
the same breed. Therefore, a single screening really rep- amino acid alanine to proline, a large amino acid with
resents only the status of the cat’s heart at that point in a ring. Cats that are homozygous for the mutation (both
time, and the most accurate screening programs require chromosomes in a pair contain the mutated gene) often
annual screening with echocardiography until at least 10 appear to develop a more severe form of hypertrophic
years of age. cardiomyopathy and may show clinical signs before 4
years of age. Cats that are heterozygous (only one of two
Recommendations chromosomes in a pair has the mutated gene) may
Clear develop the disease at a later age and have milder signs
Cats that have no auscultable murmur, gallop, or (Meurs et al. 2005). Additionally, for reasons not well
arrhythmia and have a normal echocardiographic exam understood, a small percentage of cats with the muta-
are considered to be clear of hypertrophic cardiomyopa- tion may not ever show clinical signs of the disease, and
thy at that time, but as mentioned above, should be this is referred to as decreased penetrance of disease.
evaluated annually. Genetic modifiers that affect the expression and pene-
trance of the disease are likely but have yet to be deter-
Indeterminate mined. Some Maine coon cats develop familial
It is not uncommon for adult cats to have some indica- hypertrophic cardiomyopathy in the absence of the
tion of cardiac abnormalities, including the presence of mutation of myosin binding protein C, and likely possess
an auscultable murmur in the face of a normal echocar- a different mutation that is yet to be identified.
diogram or the presence of some echocardiographic A substitution mutation has also been identified in
abnormality that does not truly meet the criteria of an the myosin binding protein C gene in the Ragdoll cat
affected cat. Some of these cats may progress to develop (Meurs et al. 2007). However, the Ragdoll mutation is
hypertrophic cardiomyopathy; others will never advance different from the Maine coon mutation and is a cyto-
at all. Therefore, cats that are classified as having an sine to thymine substitution in the 820th codon, which
indeterminate status should ideally be at least temporar- changes the amino acid produced from arginine to tryp-
ily withheld from the breeding program until their tophan. It is extremely unlikely that the Maine coon and
disease status is more certain, which is assessed by repeat Ragdoll mutations were inherited from a common
echocardiography. A recheck in 6–12 months with an ancestor since the mutations are different and are located
echocardiogram could be considered. in such different regions of the gene. It is more likely
that these are two novel mutations that developed inde-
Affected pendently. In the Ragdoll, homozygous cats appear to be
Given the heritability of the disease in at least some very severely affected with development of heart failure
breeds of cats, breeding of affected cats cannot be rec- and thromboembolic episodes often before 2 years of
ommended. Additionally, once an affected cat has been age. Heterozygous cats appear to have a much more mild
identified, the siblings and parents of the affected cat form of the disease that may include only mild papillary
should be screened by echocardiography and all off- muscle hypertrophy.
spring carefully followed echocardiographically on an In both cases, the mutations appear to be quite breed-
annual basis in order to identify affected animals as soon specific. The Maine coon mutation is specific for the
as possible. Maine coon and the Ragdoll mutation is specific for the
Ragdoll. Affected Sphynx, British shorthair, Siberian,
Bengal, and Norwegian Forest cat have been screened
GENETIC SCREENING
for, but do not have, the mutation (Meurs et al. 2009). Screening
A causative DNA mutation has now been identified in
two breeds of cats, the Maine coon and the Ragdoll Mutation Screening
(Meurs et al. 2005, 2007). Genetic testing is now available to test a cat for either
In the Maine coon, a genetic mutation has been iden- the Maine coon or Ragdoll mutation by submitting a
tified in the myosin binding protein C (MYBPC3) gene, DNA sample to a reputable screening laboratory. High-
a cardiac sarcomeric protein involved in cardiac con- quality DNA samples can be obtained either from a
traction (Meurs et al. 2005). It is also a commonly blood sample submitted in an EDTA tube or by brush-
mutated gene responsible for familial hypertrophic car- ing the buccal mucosa of the cat with a special buccal
diomyopathy in humans (Keren et al. 2008). The muta- swab, although many labs will even accept samples sub-
tion in the Maine coon results in a single base pair mitted on a cotton swab. Buccal swabbing is particularly