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

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 I _Ks, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.     

Comparison of Whole Ovary Cryotreatments for Fertility Preservation

The goal of this study was to compare a traditional slow‐freeze method (TF) with an open unidirectional slow freeze cooling system (UF) for whole ovary cryopreservation. Therefore, whole pig ovaries were randomly assigned to (A) fresh control, (B) traditional slow freeze (TF) or (C) unidirectional slow freeze (UF). Ovaries were perfused with 10% DMSO in Krebs‐Ringer. For TF, whole ovaries were placed in specimen jars containing 10% DMSO and placed into a specialized container for freezing filled with propan‐2‐ol. For UF, whole ovaries were placed within a specially designed container containing 10% DMSO and transferred to a specialized freezing machine (CTE 920). Histological evaluation demonstrated intact morphology of follicles in all groups; however, an overall decrease of follicle numbers in TF (46%) and UF (50%) compared to fresh control. Live/dead assay indicated significantly lower populations of live cells in both TF (60%) and UF (58%) compared to fresh tissue (74%). TUNEL assay confirmed a difference in percentage of apoptotic follicles between fresh and TF, but there was no significant difference between fresh and UF. To improve the structural and functional integrity of whole ovaries, further investigation, especially into directional freezing, is needed. Whole ovary cryopreservation could provide opportunities for women facing fertility loss due to chemo‐ or radiotherapy treatment.     

Starch digestion by feedlot cattle: predictions from analysis of feed and fecal starch and nitrogen

To evaluate the utility of N as a digestion marker to predict total tract starch digestion, data from 32 metabolism trials involving 147 steers and 637 individual starch digestibility measurements were compiled. All trials were conducted at the University of California Desert Research and Extension Center. Total tract starch digestibility was determined from concentrations of starch and chromic oxide in feed and feces. In all trials, the steers were adapted to diets for 10 d followed by 4 d for collection of samples of feces. During collection, fecal samples (approximately 200 g, wet basis) were obtained twice daily. Samples from each steer within each collection period were composited for analysis. Diets contained 46.5 +/- 7.4% starch and 1.85 +/- 0.20% N. Apparently digestible N as a percentage of diet DM was closely associated (r(2) = 0.73; P < 0.001) with dietary N concentration. Fecal N concentration (FN, % of DM) explained 35% of the variation in fecal DM excretion (S(y.x) = 4.3; P < 0.001). Incorporating FN into the model, starch digestion was estimated as follows: starch digestion, % of intake = 100 {1 - [(0.938 -0.497FN + 0.0853FN(2)) FS/DS]}, where FS is fecal starch concentration (% of DM) and DS is dietary starch concentration (% of DM; r(2) = 0.94; S(y.x) = 0.68; P < 0.001). Fecal starch concentration alone explained 96% of the variation (S(y.x) = 0.45; P < 0.001) in total tract starch digestion: starch digestion, % = 99.9 - 0.413FS -0.0104FS(2). Omitting cases in our data set in which observed total tract starch digestion was less than 95%, the r(2) between FS and starch digestibility decreased to 0.82 (S(y.x) = 0.26; n = 529). However, estimated starch digestion using the equation incorporating FN remained closely associated with the observed starch digestion (r(2) = 0.90; S(y.x) = 0.22; P < 0.001; n = 529). Equations also were developed to predict NE(m) and NE(g) concentrations of common feed grains based on starch digestibility and FS. Starch digestion can be accurately predicted based on FS. However, incorporation of FN into the model markedly enhanced the estimates of grain quality and the efficacy of processing when total tract starch digestion exceeded 95%.     

An outbreak of severe iodine-deficiency goitre in a sheep flock in north-east Victoria

Background Several outbreaks of goitre, considered to be related to iodine deficiency, occurred in sheep flocks throughout Victoria in 2010. Objective We describe one outbreak in Merino–Border Leicester‐cross ewes and their lambs in north‐east Victoria that appeared to be associated with increased rainfall and pasture growth, particularly during the preceding summer and autumn. Results The outbreak was characterised by a four‐fold increase in neonatal lamb deaths and goitre, alopecia and poor skeletal development in the lambs. Most cases occurred in lambs born to 2‐year‐old crossbred ewes that had grazed long, lush perennial pastures throughout their entire pregnancy, whereas few cases occurred in mature crossbred or Merino ewes that had grazed shorter, annual pastures on hill country for 3 weeks in late pregnancy but were otherwise managed similarly. Conclusion Existing recommendations for south‐eastern Australia are that only spring‐lambing ewes in iodine‐deficient areas require iodine supplementation to prevent goitre in years with high autumn–winter rainfall. Aspects of this outbreak suggest that ewes lambing at other times of the year and grazing abundant pasture for prolonged periods may also require supplementation to prevent goitre, even if autumn–winter rainfall does not exceed previously established thresholds.