A 3-mo-old domestic shorthair cat was presented with multiple fractures. Bone morphology was normal radiographically, with no long bone deformity or increased bone translucency. A bone biopsy from the ilium was examined histologically, revealing that bone matrix in the trabeculae extended from the growth plate, but cartilage remained in the distal trabeculae. Osteoblasts were observed at the bone surface via immunohistochemical detection with an anti-RUNX2 antibody. Whole-genome sequencing identified a homozygous missense mutation (valine to methionine) in the zinc-dependent metalloprotease domain of BMP1 , a gene associated with human osteogenesis imperfecta type 13. In silico analysis predicted that this mutation would disrupt BMP1 protein function, which could affect type I collagen processing. Our findings suggest that a missense mutation in BMP1 may cause feline osteogenesis imperfecta.
Takanosu et al. (Wed,) studied this question.