An ABCC9 Missense Variant Is Associated with Sudden Cardiac Death and Dilated Cardiomyopathy in Juvenile Dogs

Eva Furrow, Nicole Tate, Katie Minor, Shannon Martinson, Shannon Larrabee, Marjukka Anttila, Meg Sleeper, Paula Henthorn

Research output: Contribution to journalArticlepeer-review


Sudden cardiac death in the young (SCDY) is a devastating event that often has an underlying genetic basis. Manchester Terrier dogs offer a naturally occurring model of SCDY, with sudden death of puppies as the manifestation of an inherited dilated cardiomyopathy (DCM). We performed a genome-wide association study for SCDY/DCM in Manchester Terrier dogs and identified a susceptibility locus harboring the cardiac ATP-sensitive potassium channel gene ABCC9. Sanger sequencing revealed an ABCC9 p.R1186Q variant present in a homozygous state in all SCDY/DCM-affected dogs (n = 26). None of the controls genotyped (n = 398) were homozygous for the variant, but 69 were heterozygous carriers, consistent with autosomal recessive inheritance with complete penetrance (p = 4 × 10−42 for the association of homozygosity for ABCC9 p.R1186Q with SCDY/DCM). This variant exists at low frequency in human populations (rs776973456) with clinical significance previously deemed uncertain. The results of this study further the evidence that ABCC9 is a susceptibility gene for SCDY/DCM and highlight the potential application of dog models to predict the clinical significance of human variants.

Original languageEnglish (US)
Article number988
Issue number5
StatePublished - May 2023

Bibliographical note

Funding Information:
Funding for this research was provided through a donation from the American Manchester Terrier Club. S.L. was supported in part by a National Institutes of Health (NIH) Office of the Director Short-Term Institutional Research Training Grant, T35OD011118. E.F. was supported in part by an NIH Office of the Director Special Emphasis Research Career Award, K01OD019912, and an NIH National Center for Advancing Translational Sciences grant, UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Publisher Copyright:
© 2023 by the authors.


  • canine
  • channelopathy
  • molecular autopsy
  • sudden cardiac death in the young

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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