Categories: Skeleton phene (incl. short stature & teeth)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 616229 (trait) , 616215 (gene)

Mendelian trait/disorder: yes

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2022

Inheritance: Having no access to cats related to the affected kitten born to a stray cat, Takanosu and Kagawa (2022) rightly point out that "we cannot conclude that this disease is inherited." However, as they explain, available evidence (homozygosity for the likely causal variant; mutations in this same gene cause similar inherited disorders in humans and in mice) strongly supports autosomal recessive inheritance.

Molecular basis: Takanosu and Kagawa (2022) described a kitten born to a stray cat in Japan. Having diagnosed the kitten as being affected with osteogenesis imperfecta, the authors performed a whole-genome sequence and then searched for mutations in comparative (human) candidate genes, finding just one likely causal variant, namely a "2-bp deletion in exon 3 of CREB3L1 (c.370_371delTG). This mutation was detected in all sequenced contigs except for the vector end, which indicated homozygosity . . . . The 2-bp deletion mutation caused a frameshift and induced a premature stop codon. (p.C124fs). Sequencing of the PCR product from RT-PCR revealed a 2-bp deletion in the cDNA of CREB3L1 . . . as well."

Clinical features: Takanosu and Kagawa (2022): "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."

Pathology: Takanosu and Kagawa (2022): "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."

Prevalence: Not having access to any family samples from the affected stray cat, Takanosu and Kagawa (2022) genotyped 136 normal cats, none of which carried the likely causal variant.

Associated gene: