Vitamin D-deficiency rickets (VDDR), type 1A

Gene: CYP27B1

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 (nonsense), CYP27B1 gene; c.261 C>A, p.(Tyr87 STOP), exon2, chromosome 10.

Breed: Pug

Medical system: Skeleton

Age of onset of symptoms: 12-13 weeks.

Vitamin D is a fat-soluble vitamin involved in body calcium homeostasis, bone growth and mineralization and in the intestinal absorption of calcium, magnesium and phosphate. Lack of vitamin D, caused by genetic lesions or by dietary deficiencies, can result in rickets, a disease involving inadequately mineralized bones that are soft, weak and deformed. In two related European litters of Pugs, three puppies showed clinical signs of rickets including bone deformities, lameness, reduced bone density on X-rays and hypocalcemia. DNA analysis revealed a mutation in the CYP27B1 gene as the genetic cause of the disease. The protein product of the CYP27B1 gene normally catalyzes the kidney conversion of calcifediol, a vitamin D prohormone, into calcitriol, the active form of vitamin D. In humans, rickets due to mutations in the CYP27B1 gene is referred to as vitamin D-deficiency (VDDR) type 1A. For one affected Pug, oral supplementation of Vitamin D was able to normalize bone mineralization and calcium serum levels. Further DNA studies revealed that the parents of the affected puppies were indeed obligate carriers for the identified mutation. Although a small study of 20 control Pugs did not detect the mutation, additional DNA studies are now required to adequately determine the penetration of the mutation within the wider Pug population. In the meantime, veterinarians and breeders of Pugs should be aware of this mutation and should use DNA testing and selective breeding as required to prevent the disease, and oral vitamin D supplementation to treat the disease if it is diagnosed.

References:

OMIA link: [0837-9615]

Rohdin C, Wang C, Brander G, et al. (2023) Mutations in the CYP27B1 gene cause vitamin D dependent rickets in pugs. J Vet Interne Med. 37(4):1507-1513. [pm/37293695]

Clarke KE, Hurst EA, Mellanby RJ. (2021) Vitamin D metabolism and disorders in dogs and cats. J Small Anim Pract. 62(11):935-947. [pm/34323302]

Contributed by: Xavier Bouchard and Marc-Àndré Latreille, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal. (Translation DWS)