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Hypertrophic cardiomyopathy in young Maine Coon cats caused by the p.A31P cMyBP-C mutation--the clinical significance of having the mutation.

Godiksen MT, Granstrøm S, Koch J, Christiansen M - Acta Vet. Scand. (2011)

Bottom Line: The pattern of inheritance has been considered autosomal dominant based on a single pedigree.The fHCM prevalence was 6.3% in the cohort.As there is no significant odds ratio associated with being heterozygous for the pA31P cMyBP-C mutation at this age, the mutation must have a very low penetrance in this group.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.

ABSTRACT

Background: In Maine Coon (MC) cats the c.91G > C mutation in the gene MYBPC3, coding for cardiac myosin binding protein C (cMyBP-C), is associated with feline hypertrophic cardiomyopathy (fHCM). The mutation causes a substitution of an alanine for a proline at residue 31 (p.A31P) of cMyBP-C. The pattern of inheritance has been considered autosomal dominant based on a single pedigree. However, larger studies are needed to establish the significance of cats being heterozygous or homozygous for the mutation with respect to echocardiographic indices and the probability of developing fHCM. The objective of the present study was to establish the clinical significance of being homozygous or heterozygous for the p.A31P cMyBP-C mutation in young to middle-aged cats.

Methods: The cohort consisted of 332 MC cats, 282 cats < 4 years (85%). All cats were examined by 2-D and M-mode echocardiography. DNA was extracted from blood samples or buccal swabs and screened for the p.A31P cMyBP-C mutation in exon 3 of the gene, using polymerase chain reaction followed by DNA sequencing.

Results: The fHCM prevalence was 6.3% in the cohort. Eighteen cats were homozygous and 89 cats were heterozygous for the mutation. The odds ratio for having fHCM for homozygous cats was 21.6 (95% confidence interval 7.01-66.2) - when the group of equivocal cats was categorized as non-affected. Overall, 50% of the cats that were homozygous for the mutation had fHCM. p.A31P heterozygosity was not associated with a significant odds ratio for fHCM. In cats in the 4 to 6 years of age range a similar, non significant, odds ratio was seen in heterozygous cats. Only two cats over four years were homozygous and both were diagnosed with fHCM.

Conclusion: As there is no significant odds ratio associated with being heterozygous for the pA31P cMyBP-C mutation at this age, the mutation must have a very low penetrance in this group. From our data it would appear that most MC cats that develop fHCM due to the p.A31P mutation prior to the age of approximately 6 years do so because they are homozygous for this mutation.

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Distributions of fHCM and equivocal cases in respect to p.A31P cMyBP-C genotype status. A: Histogram of the distribution for the entire cohort. The group of p.A31P cMyBP-C homozygous cats had an increased proportion of fHCM cases. B. Histogram of the distribution for cats over 4 years of age. Except for the homozygous the distribution was very similar to the distribution shown in A. Parts of boxes marked with small dots represent fHCM negative cats. Blank parts of the boxes indicate equivocal cases. Box marked with black stripes indicate cases of fHCM.
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Figure 4: Distributions of fHCM and equivocal cases in respect to p.A31P cMyBP-C genotype status. A: Histogram of the distribution for the entire cohort. The group of p.A31P cMyBP-C homozygous cats had an increased proportion of fHCM cases. B. Histogram of the distribution for cats over 4 years of age. Except for the homozygous the distribution was very similar to the distribution shown in A. Parts of boxes marked with small dots represent fHCM negative cats. Blank parts of the boxes indicate equivocal cases. Box marked with black stripes indicate cases of fHCM.

Mentions: All cats were genotyped with respect to the cMyBP-C mutation (Table 3). Eighteen MC cats were homozygous, 89 MC cats were heterozygous and 225 MC cats were wild type (no mutation). 10 out of 21 MC cats with an fHCM diagnosis did not carry the mutation. The histogram in Figure 4A shows the fraction of fHCM and equivocal cases in the three different genotypes.


Hypertrophic cardiomyopathy in young Maine Coon cats caused by the p.A31P cMyBP-C mutation--the clinical significance of having the mutation.

Godiksen MT, Granstrøm S, Koch J, Christiansen M - Acta Vet. Scand. (2011)

Distributions of fHCM and equivocal cases in respect to p.A31P cMyBP-C genotype status. A: Histogram of the distribution for the entire cohort. The group of p.A31P cMyBP-C homozygous cats had an increased proportion of fHCM cases. B. Histogram of the distribution for cats over 4 years of age. Except for the homozygous the distribution was very similar to the distribution shown in A. Parts of boxes marked with small dots represent fHCM negative cats. Blank parts of the boxes indicate equivocal cases. Box marked with black stripes indicate cases of fHCM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3044103&req=5

Figure 4: Distributions of fHCM and equivocal cases in respect to p.A31P cMyBP-C genotype status. A: Histogram of the distribution for the entire cohort. The group of p.A31P cMyBP-C homozygous cats had an increased proportion of fHCM cases. B. Histogram of the distribution for cats over 4 years of age. Except for the homozygous the distribution was very similar to the distribution shown in A. Parts of boxes marked with small dots represent fHCM negative cats. Blank parts of the boxes indicate equivocal cases. Box marked with black stripes indicate cases of fHCM.
Mentions: All cats were genotyped with respect to the cMyBP-C mutation (Table 3). Eighteen MC cats were homozygous, 89 MC cats were heterozygous and 225 MC cats were wild type (no mutation). 10 out of 21 MC cats with an fHCM diagnosis did not carry the mutation. The histogram in Figure 4A shows the fraction of fHCM and equivocal cases in the three different genotypes.

Bottom Line: The pattern of inheritance has been considered autosomal dominant based on a single pedigree.The fHCM prevalence was 6.3% in the cohort.As there is no significant odds ratio associated with being heterozygous for the pA31P cMyBP-C mutation at this age, the mutation must have a very low penetrance in this group.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.

ABSTRACT

Background: In Maine Coon (MC) cats the c.91G > C mutation in the gene MYBPC3, coding for cardiac myosin binding protein C (cMyBP-C), is associated with feline hypertrophic cardiomyopathy (fHCM). The mutation causes a substitution of an alanine for a proline at residue 31 (p.A31P) of cMyBP-C. The pattern of inheritance has been considered autosomal dominant based on a single pedigree. However, larger studies are needed to establish the significance of cats being heterozygous or homozygous for the mutation with respect to echocardiographic indices and the probability of developing fHCM. The objective of the present study was to establish the clinical significance of being homozygous or heterozygous for the p.A31P cMyBP-C mutation in young to middle-aged cats.

Methods: The cohort consisted of 332 MC cats, 282 cats < 4 years (85%). All cats were examined by 2-D and M-mode echocardiography. DNA was extracted from blood samples or buccal swabs and screened for the p.A31P cMyBP-C mutation in exon 3 of the gene, using polymerase chain reaction followed by DNA sequencing.

Results: The fHCM prevalence was 6.3% in the cohort. Eighteen cats were homozygous and 89 cats were heterozygous for the mutation. The odds ratio for having fHCM for homozygous cats was 21.6 (95% confidence interval 7.01-66.2) - when the group of equivocal cats was categorized as non-affected. Overall, 50% of the cats that were homozygous for the mutation had fHCM. p.A31P heterozygosity was not associated with a significant odds ratio for fHCM. In cats in the 4 to 6 years of age range a similar, non significant, odds ratio was seen in heterozygous cats. Only two cats over four years were homozygous and both were diagnosed with fHCM.

Conclusion: As there is no significant odds ratio associated with being heterozygous for the pA31P cMyBP-C mutation at this age, the mutation must have a very low penetrance in this group. From our data it would appear that most MC cats that develop fHCM due to the p.A31P mutation prior to the age of approximately 6 years do so because they are homozygous for this mutation.

Show MeSH
Related in: MedlinePlus