Novel COL5A1 variants and associated disease phenotypes in dogs with classical Ehlers-Danlos syndrome
Abstract
BACKGROUND: Human patients with Ehlers-Danlos syndrome (EDS) are categorized into subtypes based on causative genetic variants and phenotypes. The classical form of EDS, primarily caused by variants in COL5A1 or COL5A2, is a very common subtype in people but is poorly characterized in dogs.
OBJECTIVE: Describe likely causal COL5A1 variants in dogs with classical EDS, summarize clinical histories, discuss potential disease mechanisms, and draw conclusions about disease prognosis.
ANIMALS: Seven client-owned dogs that exhibited clinical signs of classical EDS.
METHODS: Clinical information was recorded from medical records and communication with attending veterinarians and dog owners. To identify potential causal gene sequence variants whole-genome sequence analyses (n = 6) or Sanger sequencing (n = 1) were performed on DNA isolated from the probands. Pathological abnormalities in skin biopsy samples were assessed using histology and electron microscopy in 3 dogs.
RESULTS: Six distinct heterozygous COL5A1 sequence variants were identified. The most common clinical signs included fragile skin (n = 7), hyperextensible skin (n = 7), joint hypermobility (n = 6), and atrophic scars (n = 5). The median age at last follow-up or death was 12 years (range, 6.5-14 years). Ultrastructural abnormalities in dermal collagen differed among dogs with different COL5A1 variants.
CONCLUSION AND CLINICAL IMPORTANCE: We describe the genotypic and phenotypic spectrum of the classical subtype of EDS…
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