Categories: Homeostasis / metabolism phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 600081 (trait) , 608713 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0010810: vitamin D hydroxylation-deficient rickets, type 1B

Mendelian trait/disorder: yes

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2019

Cross-species summary: Vitamin D dependent rickets type 1B is caused by mutations in the CYP2R1 gene leading to failure of vitamin D to be converted to 25(OH)D.

History: Teshima et al. (2019): "This is the first report of type 1B vitamin D-dependent rickets in a cat."

Molecular basis: Noting that the clinical signs (see Clinical features section) of a single domestic shorthair cat were similar to those of vitamin D-dependent rickets, Teshima et al. (2019) sequenced the comparative candidate genes in this affected cat and discovered "a CYP2R1 frameshift mutation in exon 5 (where T is deleted at position c.1386). This mutation alters the amino acid sequence from position 462, while the stop codon introduced at position 481 prematurely truncates the 501 amino acid full-length protein."

Clinical features: Teshima et al. (2019) "describe the case of a 3-month-old female domestic short-haired cat previously fed on commercial kitten food that presented at our clinic with seizures, lethargy, and generalized pain. Serum and ionized calcium concentrations and 1,25-dihydroxycholecalciferol in this cat were low, and radiographs showed skeletal demineralization and abnormally wide growth plates on the long bones. Initially, simple vitamin D deficiency was suspected; however, the cat's profile, which included fed a well-balanced commercial diet, together with the findings of additional laboratory tests and the cat's unresponsiveness to various treatments, raised the suspicion of vitamin D-dependent rickets."

Breed: Domestic Shorthair.
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: