Classical Ehlers-Danlos syndrome (COL5A2-related)

Gene: COL5A2

Transmission: Autosomal dominant

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  One or both of the parents of an animal with the mutation has one or two copies of the mutation.  Animals that have one or two copies of the mutation can pass the mutation on to future generations.  Spontaneous, de novo mutations are another source of dominant genetic diseases.

Mutation: Substitution, COL5A2 gene: c.2366G>T, p.(Gly789Val), exon35, Chr.2.

Medical system: Cutaneous

Breed: Holstein

Age of onset of symptoms: Neonatal animal.

A 3-day old Holstein calf was observed to have fragile, hyperextensible skin.  Its mother was also observed to have skin laxity with scarring but was otherwise healthy. On these clinical observations a diagnosis of classical Ehlers-Danlos syndrome was made, even though hyperextension of joints was not present.  Molecular analysis was performed on the two animals, and a heterozygous mutation in the COL5A2 gene was identified that could account for the clinical signs.  The COL5A2 gene codes for a collagen protein found in connective tissues that confers tensile strength to tissues such as the skin.  Mutations in the COL5A2 gene or the closely related COL5A1 gene can be responsible for the classical Ehlers-Danlos syndrome seen in humans, dogs and cats.  In general, the occasional cases of Ehlers-Danlos observed occur due to spontaneous dominant mutations.  In a veterinary context, because affected animals can be identified soon after birth, these mutations tend not to have any breed infiltration. Thus, cases of classical Ehlers-Danlos cases although unfortunate for the individual animal should not be of undue concern to breeders.

References:

OMIA link: [2295-9913]

Roberts JH, Halper J. (2021) Connective tissue disorders in domestic animals. Adv Exp Med Biol 1348:325-335. [pm/34807427]

Jacinto JGP, Häfliger IM, Veiga IMB, et al. (2020) A Heterozygous Missense Variant in the COL5A2 in Holstein Cattle Resembling the Classical Ehlers-Danlos Syndrome. Animals (Basel) 10:2002.  [pm/33143196]

With contributions by: Charlie Savard and Agathe Beauséjour, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).