Feline vitamin D-dependent rickets type 2 caused by a missense variant in the vitamin D receptor gene.

An 11-month-old female kitten was evaluated for lameness and an inability to close her mouth. The kitten had marked hypocalcemia with elevated intact parathyroid hormone and 1,25(OH)2D3 levels. Radiographic imaging indicated generalized osteopenia and dysplasia of temporomandibular joints. Since a nutritionally complete diet was being fed, dysfunction of vitamin D receptors (VDR) was suspected. Genetic tests revealed three variants (c.439A >G, c.509C >T, and c.529_530insGCA) in the VDR gene, and c.509C >T, replacing proline 170 with leucine (p.Pro170Leu), was predicted to be damaging by in silico analysis. VDR-deficient feline kidney epithelial cells were transfected with wild-type or p.Pro170Leu VDR expression vectors, revealing impaired responsiveness to 1,25(OH)2D3 in mutants. Based on these findings, the cat was diagnosed with vitamin D-dependent rickets type 2.