Osteogenesis imperfecta (CREB3L1 related)

Gene: CREB3L1
Transmission: Autosomal, likely 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: Deletion, CREB3L1 gene; c.370_371 del.TG, p.(Cys124 frameshift STOP), exon3, chromosome D1.
Breed: Japanese Domestic
Medical system: Skeletal
Age of onset of symptoms: Shortly after birth; with growth.

Osteogenesis imperfecta refers to a family of congenital diseases involving bone fragility due to genetic errors in bone formation. The genetic lesions involve the formation and/or function of the collagen 1 protein, the major structural collagen molecule found in bones, tendons and connective tissues. Of veterinary interest, mutations in the COL1A1, COL1A2 and SERPINH1 genes have been reported in dogs, and the CREB3L1 gene is now described in cats.

A 2-month-old kitten was presented to a veterinary clinic in Japan with clinical signs including growth retardation and abnormal gait. X-rays revealed a decrease in bone density (osteoporosis), deformed long bones, and several fractures of long bones, and a diagnosis of osteogenesis imperfecta was made. Genetic analysis identified a homozygous mutation in the CREB3L1 gene, which codes for a transcription factor important in osteoblasts for the expression of the COL1A1 gene. In humans, mutations in the CREB3L1 gene are responsible for osteogenesis imperfecta type XVI. The mutation seen in the kitten was a two base pair deletion that would cause a change in reading frame and introduce a premature stop codon. This would result in the production of a truncated, non-functional transcription factor. Neither parents nor pedigree of the kitten were available for further analysis. Genotyping 136 normal cats did not detect the mutation, thus the frequency of the causal mutation in the Japanese domestic cat population remains unknown.

References:

Lien OMIA : [2533-9685]

Takanosu M, Kagawa Y. (2022) Severe osteogenesis imperfecta caused by CREB3L1 mutation in a cat. J Vet Diagn Invest 34:558-563.  [pm/35168412]

Contributed by: Kassandra Bouchard-Dion and Mariane Robitaille, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal. (Translation DWS)