Chondrodysplasia, EVC2-related

Gene: EVC2

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.

Mutations:

Mutation 1 (Japanese Brown; Wagyu): Deletion, insertion, EVC2 gene; c.2327_2328 delCA insG, p.(Ala776Gly frameshift STOP 22), chromosome 6.

Mutation 2 (Japanese Brown; Wagyu): Substitution (splicing error), EVC2 gene; c.1356 C>T, cryptic splice doner site exon11, chromosome 6.

Mutation 3 (Tirolian Grey): Deletion, EVC2 gene; c.2993_2994 delAC, p.(Asp998Glu frameshift STOP 13), exon19, chromosome 6.

Breeds: Japanese Brown, Tyrolian Grey, Wagyu

Medical system: Skeletal

Age of onset of symptoms: At birth.

Chondrodysplastic dwarfism, involving the disproportionate shortening of long bones of the limbs, is seen in a number of bovine breeds and can lead to problems in locomotion.  In affected animals there is a developmental defect in the formation of the epiphysial plates of long bones due to the accelerated differentiation of chondrocytes.  DNA studies in two breeds, the Japanese Brown, a type of Wagyu cattle, and the Tirolian Gray, a European breed, showed that the chondrodysplastic phenotype was caused by mutations in the EVC2 gene.  The EVC2 gene codes for a protein involved in the regulation of normal signaling pathways during bone formation, and mutations in the EVC2 gene are one of the causes of disproportionate dwarfism as seen in humans.  In the Japanese Brown breed, two mutations in the EVC2 gene were identified, and in a survey study of 372 animals, each mutation had a carrier frequency of 2.1%.  Dwarf animals in the Japanese Brown breed can result from homozygous single mutations or from double heterozygous mutations in the EVC2 gene.  Chondrodysplastic dwarfism seen in other cattle breeds such as the Angus are not caused by the described Japanese Brown mutations.  DNA tests are available to allow veterinarians and animal breeders to eliminate these mutations and this phenotype from their animals.

References:

OMIA link: [2540-9913]

Matsumoto H, Kimura S, Saito R, et al. (2023) Causative alleles for chondrodysplastic dwarfism, factor XI deficiency, and factor XIII deficiency in the Kumamoto sub-breed of Japanese Brown cattle. Anim Sci J 94:e13882.  [pm/37909240]

Murgiano L, Jagannathan V, Benazzi C, et al. (2014) Deletion in the EVC2 gene causes chondrodysplastic dwarfism in Tyrolean Grey cattle. PLoS One 9:e9486.  [pm/24733244]

Takeda H, Takami M, Oguni T, et al. (2002) Positional cloning of the gene LIMBIN responsible for bovine chondrodysplastic dwarfism Proceedings of the National Academy of Sciences of the United States of America 99:10549-10554.  [pm/12136126]

Contributed by: Emmy Barthe and Anabelle Garneau, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)