A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-02-04

AUTHORS

Kathryn M. Meurs, Steven G. Friedenberg, Justin Kolb, Chandra Saripalli, Paola Tonino, Kathleen Woodruff, Natasha J. Olby, Bruce W. Keene, Darcy B. Adin, Oriana L. Yost, Teresa C. DeFrancesco, Sunshine Lahmers, Sandra Tou, G. Diane Shelton, Henk Granzier

ABSTRACT

The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (PDK4) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the PDK4 variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the PDK4 variant was performed. A pathologic missense variant in the titin gene located in an immunoglobulin-like domain in the I-band spanning region of the molecule was identified and was highly associated with the disease (p < 0.0001). We demonstrate here the identification of a variant in the titin gene highly associated with the disease in this spontaneous canine model of dilated cardiomyopathy. This large animal model of familial dilated cardiomyopathy shares many similarities with the human disease including mode of inheritance, clinical presentation, genetic heterogeneity and a pathologic variant in the titin gene. The dog is an excellent model to improve our understanding of the genotypic phenotypic relationships, penetrance, expression and the pathophysiology of variants in the titin gene. More... »

PAGES

1-10

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00439-019-01973-2

DOI

http://dx.doi.org/10.1007/s00439-019-01973-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111918385

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30715562


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