OMIA:000837-9615 : Vitamin D-deficiency rickets, type IA in Canis lupus familiaris (dog)

In other species: domestic cat , pig

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

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 264700 (trait) , 609506 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2023

Cross-species summary: Vitamin D (cholecalciferol) is synthesised in the skin from 7-dehydrocholesterol by the action of UV radiation from sunlight. Cholecalciferol, however, has very little biological activity: it requires two hydroxylations in order to become (biologically) active. The first hydroxylation, catalysed by cholecalciferol 25-hydroxylase, occurs in the liver. The second of these hydroxylations occurs in the kidney under the action of the enzyme 25-alpha-hydroxycholecalciferol 1-hydroxylase. The resultant active form of vitamin D (called 1,25-dihydroxycholecalciferol or 1,25(OH)sub2D) is a steroid hormone that plays a vital role in whole-body calcium homeostasis. Vitamin D-deficieny rickets, type 1A (previously known as Pseudo-vitamin D deficiency rickets) is an inherited deficiency of the 1-hydroxylase enzyme, due to mutations in the gene that encodes this enzyme, namely CYP27B1. As expected, this deficiency results in clinical signs indistinguishable from those seen in individuals suffering from non-genetic lack of vitamin D, most commonly resulting from a dietary deficiency of calcium or insufficient exposure to sunlight. The clinical signs of rickets (inherited and non-genetic) arise from defects in calcium homeostasis. The most noticeable effects include a failure of calcification of bones (leading to bowing of limbs) and delayed dentition.

Species-specific symbol: VDDR type 1A

Molecular basis: Rhodin et al. (2023) "A truncating mutation in the 1α-hydroxylase gene (CYP27B1) was identified by genome sequence analysis of the pugs with VDDR type 1A."

Clinical features: Rhodin et al. (2023) investigated related pugs from 2 litters: "Three pugs had clinical signs including, lameness, bone deformities, and dyspnea. One other pug was found dead. Radiographs of 2 affected pugs, 5 and 6 months old, showed generalized widening, and irregular margination of the physes of both the appendicular and the axial skeleton with generalized decrease in bone opacity and bulbous swelling of the costochondral junctions. Two pugs had low serum calcium and 1,25 (OH)2D3 concentrations. Test results further indicated secondary hyperparathyroidism with adequate concentrations of 25-hydroxyvitamin D."

Pathology: Rhodin et al. (2023) "Necropsy [of affected pugs] revealed tongue-like projections of cartilage extending into the metaphysis consistent with rickets, loss of metaphyseal mineralization and lung pathology."

Breed: Pug (Dog) (VBO_0201089).
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:

Symbol Description Species Chr Location OMIA gene details page Other Links
CYP27B1 cytochrome P450, family 27, subfamily B, polypeptide 1 Canis lupus familiaris 10 NC_051814.1 (1840136..1834457) CYP27B1 Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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 Year Published PubMed ID(s) Acknowledgements
1576 Pug (Dog) Vitamin D-deficiency rickets, type IA CYP27B1 nonsense (stop-gain) Naturally occurring variant UU_Cfam_GSD_1.0 10 g.2182971G>T c.261C>A p.(Y87*) XM_038549826.1; XP_038405754.1 2023 37293695

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000837-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2023 Rohdin, C., Wang, C., Brander, G., Rondahl, V., Karlsson, Å., Friling, L., Fischetti, A., Meadows, J., Häggström, J., Jäderlund, K.H., Ljungvall, I., Lindblad-Toh, K. :
Mutations in the CYP27B1 gene cause vitamin D dependent rickets in pugs. J Vet Intern Med , 2023. Pubmed reference: 37293695. DOI: 10.1111/jvim.16791.
2021 Clarke, K.E., Hurst, E.A., Mellanby, R.J. :
Vitamin D metabolism and disorders in dogs and cats. J Small Anim Pract 62:935-947, 2021. Pubmed reference: 34323302. DOI: 10.1111/jsap.13401.
1988 Johnson, K.A., Church, D.B., Barton, R.J., Wood, A.K.W. :
Vitamin D-dependent rickets in a Saint Bernard dog Journal of Small Animal Practice 29:657 - 666, 1988.

Edit History

  • Created by Frank Nicholas on 04 Apr 2010
  • Changed by Imke Tammen2 on 10 Jun 2023