Hypertrophic Cardiomyopathy (Sphynx type)

 

Gene : ALMS1

Transmission : Autosomal, probably recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation : Substitution, ALMS1 gene; c.7384 G>C, p.(G2462R), exon12

Medical system: Cardiac

Breeds : American Shorthair, Exotic Shorthair, Munchkin, Scottish Fold, Sphynx

Age of onset of symptoms : 1 year to 14 years (mean age 5 years)

Hypertrophic cardiomyopathy is the most common heart disease in cats and it is estimated that up to 15% of cats will suffer from this disease. In hypertrophic cardiomyopathy the heart muscle is enlarged and left ventricular walls are thickened and not dilated. In general, hypertrophic cardiomyopathy affects young cats as a genetic disease and older cats as a secondary condition due to diseases such as hyperthyroidism. In humans, mutations in multiple genes are responsible for hypertrophic cardiomyopathy and this is likely to also be the case for cats. At present, mutations in the M4BPC3 gene, affecting contraction of the heart muscle, are a known cause of hypertrophic cardiomyopathy in the Ragdoll and Maine Coon breeds of cat. More recently a mutation in the ALMS1 gene, affecting cardiac cell development and cell cycle regulation, was identified and correlated with hypertrophic cardiomyopathy in the Sphynx breed of cat. The mutation in the ALMS1 gene displays variable disease penetrance and does not explain all of the cases of hypertrophic cardiomyopathy seen in the Sphynx breed.

Note that hypertrophic cardiomyopathy in the cat has complex genetics with a number of known gene mutations involved as well as unknown mutations yet to be identified.  Characterized mutations include:

MYBPC3 gene mutations, Maine Coon and Ragdoll.  OMIA link: [0515-9685]

ALMS1 gene mutation, Sphynx.  OMIA link: [2316-9685]
MYH7 gene mutation reported in a domestic shorthair cat.  OMIA link [2122-9685]

 

References:

OMIA link:  [2316-9685]

Boeykens F, Abitbol M, Anderson H, et al. (2024) Classification of feline hypertrophic cardiomyopathy-associated gene variants according to the American College of Medical Genetics and Genomics guidelines. Front Vet Sci 11:1327081.  [pm/38371598]

Akiyama N, Suzuki R, Saito T, et al. (2023) Presence of known feline ALMS1 and MYBPC3 variants in a diverse cohort of cats with hypertrophic cardiomyopathy in Japan. PLoS One 18:e0283433.  [pubmed/37071642]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

Kittleson MD, Côté E. (2021) The feline cardiomyopathies: 2. Hypertrophic cardiomyopathy. J Feline Med Surg 23:1028-1051. [pubmed/34693811]

Kittleson MD, Côté E. (2021) The feline cardiomyopathies: 1. General concepts. J Feline Med Surg 23:1009-1027. [pubmed/34693806]

Meurs KM, Williams BG, DeProspero D, et al. (2021) A deleterious mutation in the ALMS1 gene in a naturally occurring model of hypertrophic cardiomyopathy in the Sphynx cat. Orphanet J Rare Dis 16:108. [pubmed/33639992]

O’Donnell K, Adi D, Atkins CE, et al. (2021) Absence of known feline MYH7 and MYBPC3 variants in a diverse cohort of cats with hypertrophic cardiomyopathy. Anim Genet 52:542-4. [pubmed/33970514]

Gil-Ortuño C, Sebastián-Marcos P, Sabater-Molina M, et al. (2020) Genetics of feline hypertrophic cardiomyopathy. Clin Genet 98:203-14. [pubmed/32215921]

McNamara JW, Schuckman M, Becker RC, Sadayappan S. (2020) A novel homozygous intronic variant in TNNT2 associates with feline cardiomyopathy. Front Physiol 11:608473. [pubmed/33304277]

Schipper T, VanPoucke M, Sonck L, et al. (2019) A feline orthologue of the human MYH7 c.5647G>A (p.(Glu1883Lys)) variant causes hypertrophic cardiomyopathy in a Domestic Shorthair cat. Eur J Hum Genet 27:1724-1730.  [pubmed/31164718]

 

Contribution : Judith Baillet and Constance Chalifoux , Class of 2028, Faculty of Veterinary Medicine, University of Montreal.