Dilated Cardiomyopathy (PLN related)

 

Gene: PLN

Transmission : Autosomal, dominant, with incomplete penetration

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease. Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation. One or both of the parents of an animal with the mutation has one or two copies of the mutation. Animals that have one or two copies of the mutation can pass the mutation on to future generations.

Mutation: Substitution, PLN gene; c.26 G>A, p.(R9H), exon1, chr.1.

Medical system: Cardiac

Breeds: Welsh Springer Spaniel

Age of onset of symptoms: Variable, between 1 and 8 years

Dilated cardiomyopathy (DCM) is a common primary heart disease seen in several breeds of dog with both genetic and environmental causes. The genetics of DCM is complex, with several genes and mutations contributing to a juvenile or adult-onset disease that can display either dominant or recessive heredity.  As a result of the genetic mutation, heart muscle cells function inefficiently which in turn results in compensatory ventricle dilatation, inefficient contraction, and heart arrhythmias.   Clinical signs of DCM include sudden death due to the arrhythmias or prolonged congestive heart failure with exercise intolerance, fatigue, coughing, difficulty breathing, weight loss, fluid accumulation in the abdomen, and fainting.  In terms of comparison, mutations in over 60 genes have been associated with a high risk of dilated cardiomyopathy in humans.

The PLN gene in the Welsh Springer Spaniel plays a critical role in the regulation of calcium in heart cells. A mutation in this gene causes cardiac arrhythmias and can result in sudden death. 

Mutations in additional genes that can be risk factors or be responsible for DCM in the dog:

PLN gene, OMIA link: [2195-9615]

PDK4 gene, OMIA link: [0162-9615]

TTN gene, OMIA link: [0162-9615]

RBM20 gene, OMIA link: [2365-9615]

LMNA gene, OMIA link: [2796-9615]

 

References:

OMIA link: [2195-9615]

Rivas VN, Stern JA, Ueda Y. (2023) The role of personalized medicine in companion animal cardiology. Vet Clin North Am Small Anim Pract.  [pubmed/37423841]

Gaar-Humphreys KR, Spanjersberg TCF, Santarelli G, et al. (2022) Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model. Animals (Basel) 12(13):1679.  [pubmed/35804579]

Yost,O, Friedenberg SG, Jesty SA et al. (2019) The R9H phospholamban mutation is associated with highly penetrant dilated cardiomyopathy and sudden death in a spontaneous canine model. 697:118-122, 2019. [pubmed/30794913]