OMIA 000837-9685 : Vitamin D-deficiency rickets, type I in Felis catus

In other species: dog , pig

Possibly relevant human trait(s) and/or gene(s) (MIM number): 264700

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2009

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 I (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.

Molecular basis: Giesen et al. (2009) reported an affected cat with two mutations in the CYP27B1 gene: a missense mutation (Val75Met) and a single base deletion (731delG), the latter of which is more likely to be the cause of the clinical signs. Grahn et al. (2012) reported a second causative mutation also in exon 4 of the same gene: "exon 4 G637T nonsense mutation results in a premature protein truncation, changing a glutamic acid to a stop codon, E213X, likely causing the clinical presentation of rickets."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CYP27B1 cytochrome P450, family 27, subfamily B, polypeptide 1 Felis catus B4 NC_018729.3 (86183305..86177593) CYP27B1 Homologene, Ensembl, NCBI gene

Variants

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Vitamin D-deficiency rickets, type I CYP27B1 deletion, small (<=20) c.731delG 2009 19138382
Vitamin D-deficiency rickets, type I CYP27B1 nonsense (stop-gain) Felis_catus_6.2 B4 g.86472505G>T c.637G>T p. E213* 2012 22553308 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

References


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.
2012 Grahn, R.A., Ellis, M.R., Grahn, J.C., Lyons, L.A. :
A novel CYP27B1 mutation causes a feline vitamin D-dependent rickets type IA. J Feline Med Surg 14:587-90, 2012. Pubmed reference: 22553308. DOI: 10.1177/1098612X12446637.
2011 MacKenzie, J.M., Crawford, J., Ghantous, S. :
Successful therapy of vitamin D-dependant rickets in a kitten. J Am Anim Hosp Assoc 47:290-3, 2011. Pubmed reference: 21673332. DOI: 10.5326/JAAHA-MS-5610.
2009 Geisen, V., Weber, K., Hartmann, K. :
Vitamin D-dependent hereditary rickets type I in a cat. J Vet Intern Med 23:196-9, 2009. Pubmed reference: 19138382. DOI: 10.1111/j.1939-1676.2008.00220.x.

Edit History


  • Created by Frank Nicholas on 20 Jul 2011
  • Changed by Frank Nicholas on 07 Oct 2011
  • Changed by Frank Nicholas on 17 Nov 2011
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  • Changed by Frank Nicholas on 24 Nov 2012
  • Changed by Frank Nicholas on 07 Dec 2012