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Animal genetics
Apr, 2025;56 (2): e70003.

A frameshift variant in the SLC6A5 gene is associated with startle disease in a family of Old English Sheepdogs.

Fr��derique Boeykens, Michelle Hermans, Laura Adant, Bert De Jonge, Koen Chiers, Kenny Bossens, Bart J G Broeckx
Author Information
  1. Fr��derique Boeykens: Laboratory of Animal Genetics, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. ORCID
  2. Michelle Hermans: Nesto Veterinary Referral Center Orion, Herentals, Belgium.
  3. Laura Adant: Laboratory of Animal Genetics, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
  4. Bert De Jonge: Laboratory of Pathology, Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
  5. Koen Chiers: Laboratory of Pathology, Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
  6. Kenny Bossens: Nesto Veterinary Referral Center Orion, Herentals, Belgium.
  7. Bart J G Broeckx: Laboratory of Animal Genetics, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
PMID: 40012122 DOI: 10.1111/age.70003

Abstract

A 2-week-old litter of three Old English Sheepdog puppies presented with episodic generalised muscle hypertonia and cyanosis triggered by touch and noise. Owing to poor response to therapy and progression of symptoms, the puppies were euthanised. Post-mortem histology revealed perineuronal incrustations in the spinal cord, suggestive of ischemia or neuronal necrosis. Clinical symptoms, combined with necropsy and histopathology findings, led to a suspicion of startle disease, prompting a referral to a specialised clinical genetics centre. Whole exome sequencing (WES) of the nuclear family identified a homozygous truncating variant in the SLC6A5 gene in affected individuals, with both unaffected parents being heterozygous. Additional population screening found three phenotypically unaffected carriers, indicating that the variant segregates within the Old English Sheepdog breed. This raises concerns about the management of carriers and their breeding contributions if not properly guided by DNA testing. This study addresses a frameshift variant SLC6A5:c.1322del found in Old English Sheepdogs. Next to this, the value of genetic counselling and clinical genetics services in breeding programmes is highlighted to identify carriers and guide informed breeding decisions. Finally, the findings demonstrate the utility of WES in veterinary diagnostics and provide practical insights for breeders, veterinarians and geneticists to improve the health and welfare of Old English Sheepdogs.

Keywords

canine genetics clinical genetics genetic counselling hyperekplexia startle disease whole exome sequencing

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Grants

  1. /Fund Albert & Oscar
  2. 01N04119/Bijzonder Onderzoeksfonds UGent
  3. /Advice Center Clinical Genetics

MeSH Term

Animals
Dogs
Dog Diseases
Frameshift Mutation
Female
Male
Pedigree
Exome Sequencing
GABA Plasma Membrane Transport Proteins

Chemicals

GABA Plasma Membrane Transport Proteins
Journal Article Case Reports

Word Cloud

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