OMIA 002533-9685 : Osteogenesis imperfecta, CREB3L1-elated in Felis catus

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 616229 (trait) , 616215 (gene)

Mendelian trait/disorder: yes

Considered a defect: 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:

Symbol Description Species Chr Location OMIA gene details page Other Links
CREB3L1 cAMP responsive element binding protein 3-like 1 Felis catus D1 NC_058377.1 (98361436..98396751) CREB3L1 Homologene, Ensembl, NCBI gene

Variants

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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1428 Domestic Shorthair Osteogenesis imperfecta CREB3L1 deletion, small (<=20) Naturally occurring variant Felis_catus_9.0 D1 g.100436508_100436509del c.370_371del p.(C124Lfs) XM_003993204.4; XP_003993253.1; published as c.370_371delTG 2022 35168412

Reference


2022 Takanosu, M., Kagawa, Y. :
Severe osteogenesis imperfecta caused by CREB3L1 mutation in a cat. J Vet Diagn Invest :10406387221081227, 2022. Pubmed reference: 35168412. DOI: 10.1177/10406387221081227.

Edit History


  • Created by Frank Nicholas on 24 Feb 2022
  • Changed by Frank Nicholas on 24 Feb 2022
  • Changed by Frank Nicholas on 25 Feb 2022