Sudden Death Associated with QT Interval Prolongation and KCNQ1 Gene Mutation in a Family of English Springer Spaniels

W. A. Ware, Y. Reina-Doreste, Joshua A Stern, K. M. Meurs

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: A 5-year-old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3 offspring also died suddenly. Hypothesis: Abnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family. Animals: Four remaining dogs from the affected litter and 11 related dogs. Methods: Physical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs. Results: Three of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T-wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure. Conclusions and Clinical Importance: This family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current IKs, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.

Original languageEnglish (US)
Pages (from-to)561-568
Number of pages8
JournalJournal of Veterinary Internal Medicine
Volume29
Issue number2
DOIs
StatePublished - Mar 1 2015

Fingerprint

Sudden Death
Dogs
death
mutation
Mutation
dogs
Genes
genes
DNA Sequence Analysis
litters (young animals)
Electrocardiography
Romano-Ward Syndrome
sequence analysis
Long QT Syndrome
Ambulatory Electrocardiography
arrhythmia
puppies
Threonine
protein structure
blood serum

Keywords

  • Long QT Syndrome

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Sudden Death Associated with QT Interval Prolongation and KCNQ1 Gene Mutation in a Family of English Springer Spaniels. / Ware, W. A.; Reina-Doreste, Y.; Stern, Joshua A; Meurs, K. M.

In: Journal of Veterinary Internal Medicine, Vol. 29, No. 2, 01.03.2015, p. 561-568.

Research output: Contribution to journalArticle

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N2 - Background: A 5-year-old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3 offspring also died suddenly. Hypothesis: Abnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family. Animals: Four remaining dogs from the affected litter and 11 related dogs. Methods: Physical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs. Results: Three of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T-wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure. Conclusions and Clinical Importance: This family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current IKs, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.

AB - Background: A 5-year-old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3 offspring also died suddenly. Hypothesis: Abnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family. Animals: Four remaining dogs from the affected litter and 11 related dogs. Methods: Physical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs. Results: Three of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T-wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure. Conclusions and Clinical Importance: This family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current IKs, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.

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