The R9H phospholamban mutation is associated with highly penetrant dilated cardiomyopathy and sudden death in a spontaneous canine model

• Published in: Gene 2019-05, Vol.697, p.118-122
• Main Authors: Yost, Oriana, Friedenberg, Steven G., Jesty, Sophy A., Olby, Natasha J., Meurs, Kathryn M.
• Format: Article
• Language: English
• Subjects: Canine; Dilated cardiomyopathy; Genetic; Phospholamban; Sudden death
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2019.02.022

Causative mutations for familial dilated cardiomyopathy (DCM) have been identified in the phospholamban gene. There are many poorly understood aspects about familial DCM (variable penetrance, expression) which may be studied in natural animal models. We characterized genetic aspects of familial DCM in a canine model with a high incidence of sudden death. A missense G > A mutation in exon 1 of the phospholamban gene that changed an amino acid from arginine to histidine was identified in affected dogs. This variant was predicted to be deleterious. We describe a spontaneous canine model of familial DCM and sudden death with the R9H mutation. In comparison to a reported human family, the variant was highly penetrant and resulted in sudden death. Genetic penetrance of this mutation may be influenced by genetic or environmental modifiers. The dog provides an excellent model in which to study complex aspects of familial DCM. •Dilated cardiomyopathy with sudden death was identified in Welsh Springer Spaniels.•A missense G > A mutation in exon 1 of the phospholamban gene was identified in affected dogs.•The variant changed the predicted amino acid from arginine to histidine at codon 9, (R9H).•The dog provides an excellent model to study complex aspects of this familial human disease.