Severe osteogenesis imperfecta caused by CREB3L1 mutation in a cat

Abstract

We examined the clinical features and pathology, and identified the causative mutation, of osteogenesis imperfecta in a 2-mo-old kitten with growth retardation and abnormal gait. Blood and radiographic examinations were performed on presentation. Radiographs revealed decreased opacity of numerous bones. Fractures were observed in some long bones, including femur and tibia. Histologic examination of the tibia showed decreased osteoid and osteoblasts at the primary spongiosa extending from the growth plate. The periosteum was thickened, and cortical bone and osteoblasts were decreased. Consequently, osteogenesis imperfecta was diagnosed. Genomic DNA and total RNA were extracted from the skin and used for PCR. Whole-genome sequencing identified a 2-bp deletion (c.370_371delTG; p.C124fs), which resulted in a homozygous frameshift mutation on exon 3 of CREB3L1. This mutation introduced a premature stop codon, suggesting production of the truncated protein without a functional domain as a transcription factor for expression of COL1A1 mRNA. This error may have affected collagen fibril formation, leading to the development of osteogenesis imperfecta.