OMIA 002254-9615 : Glucocorticoid resistance in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 615962

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Molecular basis: Yamanaka et al. (2019) "discovered a mutant GR [glucocorticoid receptor, now named NR3C1] in a dog suspected to have iatrogenic Cushing syndrome. The mutant GR had [69] extra nucleotides between exons 6 and 7, resulting in a truncated form of GR that was 98 amino acids shorter than the wild-type dog GR. The truncated GR exhibited very low reactivity to prednisolone, irrespective of concentration."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
NR3C1 nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) Canis lupus familiaris 2 NC_051806.1 (38692463..38573084) NR3C1 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.

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
Mixed breed Glucocorticoid resistance NR3C1 insertion, gross (>20) 2 c.2032_2033ins69 An insertion of "69 nucleotides between nucleotides 2032 and 2033 compared with dog wild type GR [i.e. NR3C1]. These extra 69 nucleotides matched a part of the nucleotide sequence of dog genomic DNA corresponding to intron 6 . . . . Insertion of these extra 69 nucleotides between exons 6 and 7 introduced a frameshift and a premature termination codon (TGA) 15 bp downstream of the insertion. This insertion is thus predicted to result in a truncated protein of 682 amino acids, compared to the normal (wild type) 780 amino acids" (Yamanaka et al., 2019) 2019 31651346

Reference


2019 Yamanaka, K., Okuda, M., Mizuno, T. :
Functional characterization of canine wild type glucocorticoid receptor and an insertional mutation in a dog. BMC Vet Res 15:363, 2019. Pubmed reference: 31651346. DOI: 10.1186/s12917-019-2129-9.

Edit History


  • Created by Frank Nicholas on 18 Mar 2020
  • Changed by Frank Nicholas on 18 Mar 2020
  • Changed by Frank Nicholas on 15 May 2020