Dwarfism (B4GALT7-related)

Gene: B4GALT7

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: Substitution, B4GALT7 gene: c.50G>A, p.(Arg17Lys), exon1, Chr.14.

Medical system: Skeletal, muscular

Breed: Friesian horse

Age of onset of symptoms: From birth.

The Friesian breed of horse is a light draught horse originating from the Netherlands.  With mechanisation after the Second World War, population numbers plummeted, resulting in genetic bottlenecks in the breed with associated medical disorders.  An autosomal recessive hereditary disorder of disproportionate dwarfism is known to be associated with the breed.  Affected animals have short legs, rib deformities, hypermobile joints, poorly developed musculature and display poor growth.  Chondrodysplasia involving disorganized growth plates of the long bones is a feature.  In 2008 it was estimated that 0.25 % of the breed was affected, corresponding to a silent carrier frequency of about one in ten animals for the breed population.

Molecular studies of dwarf Friesian horses identified a mutation in the B4GALT7 gene as being responsible for the phenotype.  The B4GALT7 gene codes for an enzyme important in the formation of extracellular proteoglycan molecules, which are themselves important for proper cartilage formation within the growth plates of long bones.  A mutation in the B4GALT7 gene that interferes with proper cartilage growth and disrupts endochondral bone formation would explain the chondrodysplasia phenotype seen in the dwarf Friesian horse.  Mutations in the B4GALT7 gene are a cause of Ehlers-Danlos syndrome seen in humans, which displays phenotypes similar to those seen in the dwarf Friesian horse.

A DNA test for the mutation is now available that will allow Friesian breeders and veterinarians to identify carrier animals within the breed. Thus, through selective mating, the dwarfism caused by the B4GALT7 mutation can be bred out of the breed.  This selective breeding must be done with care so as not to cause further genetic bottlenecks resulting in additional genetic problems for the breed.

References:

OMIA link: [2068-9796]

Durward-Akhurst SA, Marlowe JL, Schaefer RJ, et al. (2024) Predicted genetic burden and frequency of phenotype-associated variants in the horse. Sci Rep 14:8396. [pm/38600096]

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]

Leegwater PA, Vos-Loohuis M, Ducro, BJ, et al. (2016) Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7. BMC Genomics 17:839.  [pm/27793082]

Back W, van der Lugt JJ, Nikkels PG, et al. (2008) Phenotypic diagnosis of dwarfism in six Friesian horses. Equine Vet J 40:282-7. [pm/18267883]

With contributions by: Nouha Essadri and Leanna Dhanoa, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).