Also known as Mitral Regurgitation, Degenerative Mitral Valve Disease, Endocardiosis
Affected gene: NEBL3
Mode of inheritance: Autosomal recessive with incomplete penetrance
OMIA reference: 002688-9615


Applicable breed for testing:
Cavalier King Charles Spaniel
Description and clinical relevance
Genetic variants at the NEBL3 (nebulette) locus have been associated with increased severity of myxomatous mitral valve disease (MMVD) in the Cavalier King Charles Spaniel. The NEBL3 gene encodes a protein involved in myofibrillar structure and the maintenance of cardiac muscle integrity.
Dogs carrying these variants may exhibit a more pronounced progression of MMVD; however, clinical expression varies widely between individuals. 
Due to incomplete penetrance, not all genetically at-risk dogs will develop clinical signs, or they may do so to varying degrees.
Clinical manifestations are consistent with those typically observed in MMVD and may include heart murmurs, exercise intolerance, and, in advanced cases, signs of congestive heart failure. This genetic test serves as a risk assessment tool and should be interpreted alongside clinical and echocardiographic evaluations. It does not replace routine cardiac screening.
Reference:
Mead SE, Beijerink NJ, O’Brien M, Wade CM. Genetic Variants at the Nebulette Locus Are Associated with Myxomatous Mitral Valve Disease Severity in Cavalier King Charles Spaniels. Genes. 2022;13(12):2292. PubMed: 36553559.