Dermatosparaxis, Ehlers-Danlos syndrome, dEDS (ADAMTS2-related)

Gene: ADAMTS2

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Insertion ADAMTS2 gene: c.698 ins.C, p.(S235Q frameshift STOP 3), Chr.A1

Medical system: Dermal

Breed: Domestic Cat shorthair

Age of onset of symptoms: From a young age.

The Ehlers-Danlos syndrome is a group of genetic disorders seen in numerous animal species involving defects in connective tissues.   It involves errors in the maturation of collagen fibers and can be caused by multiple genetic defects.   Dermatosparaxis (“sparaxis”, to tear) is a type of Ehlers-Danlos syndrome that involves defective collagen fibers (collagen dysplasia) within the skin, resulting in thin, fragile skin with increased mobility but poor tensile resistance as well as poor wound healing.

Four domestic shorthair kittens from a related pedigree of European farm cats were presented displaying clinical signs consistent with the dermatosparaxis form of Ehlers-Danlos syndrome.  Molecular analysis revealed a homozygous frame shift mutation in the ADAMTS2 gene.  The product of the ADAMTS2 gene is an extracellular enzyme involved in collagen maturation.  Ultra-structural defects in collagen were seen in tissues from the effected animals.  In 31 local cats screened for the mutation, 20 were shown to be asymptomatic carriers.  This particular mutation of the ADAMTS2 gene can be considered a spontaneous allele amplified locally due to inbreeding events.

Mutations in the ADAMTS2 gene are the cause of recessive Ehlers-Danlos syndrome as seen in several dog breeds.  Multiple mutations in the COL5A1 gene are responsible for the dominant classical Ehlers-Danlos syndrome seen in cats, and in several dog breeds. In addition, a mutation in the COL5A2 gene is responsible for dominant Ehlers-Danlos syndrome as identified in Chihuahuas and in Holstein cattle.

References:

OMIA link: [0328-9685]

Lyons LA. (2024) Genetic testing: practical dos and don’ts for cats.  J Feline medicine and surgery 26:1-13.  [pm/39648935]

Simon R, Kiener S, Thom N, et al. (2023) Identification of an ADAMTS2 frameshift variant in a cat family with Ehlers-Danlos syndrome. G3 (Bethesda) 13:jkad152. [pm/37462293]

Vroman R, Malfait AM, Miller RE, et al. (2021) Animal models of Ehlers-Danlos syndromes: Phenotype, pathogenesis, and translational potential. Front Genet 12:726474. [pm/34712265]

With contributions by: Lola Kokta-Gagnon and Léa Bolduc, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).