OMIA 000364-9685 : Factor XII deficiency in Felis catus

In other species: dog , killer whale , bottlenosed dolphin

Possibly relevant human trait(s) and/or gene(s) (MIM number): 234000

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2015

Inheritance: Kier et al. (1980) provided evidence of autosomal recessive inheritance and reported the establishment of a colony at the University of North Carolina at Chapel Hill, derived from a gift of breeding animals from a colony established at Kansas University by Dr Bresnahan (Bender et al., 2015).

Molecular basis: Bender et al. (2015) characterised the obvious functional and comparative candidate gene for this disorder, namely the gene for factor XII, in cats: "Fourteen exons ranging in size from 57 to 222 base pairs were confirmed spanning 8 Kb on chromosome A1. The 1828–base pair feline FXII messenger RNA (mRNA) sequence contains an open reading frame that encodes a protein of 609 amino acids with high homology to human FXII protein." Subsequent sequencing in normal and affected cats identified a "single base deletion in exon 11 of the FXII coding gene in our colony of cats results in deficient FXII activity. Translation of the mRNA transcript shows a frame shift at L441 (C441fsX119) resulting in a nonsense mutation and a premature stop codon with a predicted 560–amino acid protein. The mutant FXII protein is truncated in the 3′ proteolytic light chain region of the C-terminus, explaining its loss of enzymatic activity."

By sequencing the most likely candidate gene in 6 Japanese domestic short-hair cats (2 cats with severely reduced FXII activity (7.1 % and 9.3 %, respectively) and 4 cats with moderately reduced FXII activity (range 36.0 to 46.3 %)), Maruyama et al. (2017) identified a new likely causal variant in exon 13 of the F12 gene: "Cats with severely reduced FXII activity were homozygous" for a missense mutation c.1631G>C, p.G544A; "Cats with moderately reduced FXII activity were heterozygous for this mutation". These authors also reported that "Expression studies revealed reduced secretion of p.G544A mutant FXII protein from transfected HEK293 cells compared with wild type FXII."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
F12 coagulation factor XII (Hageman factor) Felis catus A1 NC_018723.3 (175374296..175382370) F12 Homologene, Ensembl, NCBI gene

Variants

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.

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
Factor XII deficiency F12 deletion, small (<=20) c.1321delC p.C441fsX119 2015 24793828
Domestic shorthair Factor XII deficiency F12 missense Felis_catus_6.2 A1 g.173159981G>C c.1631G>C p.G544A 2017 28392508 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.
2019 Maruyama, H., Brooks, M.B., Stablein, A., Frye, A. :
Factor XII deficiency is common in domestic cats and associated with two high frequency F12 mutations. Gene :, 2019. Pubmed reference: 31022435. DOI: 10.1016/j.gene.2019.04.053.
2017 Maruyama, H., Hosoe, H., Nagamatsu, K., Kano, R., Kamata, H. :
A novel missense mutation in the factor XII gene in a litter of cats with factor XII deficiency. J Vet Med Sci :, 2017. Pubmed reference: 28392508. DOI: 10.1292/jvms.16-0602.
2015 Bender, D.E., Kloos, M.T., Pontius, J.U., Hinsdale, M.E., Bellinger, D.A. :
Molecular characterization of cat factor XII gene and identification of a mutation causing factor XII deficiency in a domestic shorthair cat colony. Vet Pathol 52:312-20, 2015. Pubmed reference: 24793828. DOI: 10.1177/0300985814532821.
2006 Brooks, M., Dewilde, L. :
Feline factor XII deficiency. Compend. Contin. Educ. Pract. Vet. 28:148-156, 2006.
1990 Kier, A.B., Mcdonnell, J.J., Stern, A., Ratnoff, O.D. :
The Arthus Reaction in Cats Deficient in Hageman Factor (Factor-XII) Journal of Comparative Pathology 102:33-47, 1990. Pubmed reference: 2138171.
1988 Fogh, J.M., Fogh, I.T. :
Inherited coagulation disorders. Vet Clin North Am Small Anim Pract 18:231-43, 1988. Pubmed reference: 3282382.
Parker, M.T., Collier, L.L., Kier, A.B., Johnson, G.S. :
Oral Mucosa Bleeding Times of Normal Cats and Cats with Chediak-Higashi Syndrome or Hageman Trait (Factor XII Deficiency). Vet Clin Pathol 17:9-12, 1988. Pubmed reference: 15162339.
1980 Kier, A.B., Bresnahan, J.F., White, F.J., Wagner, J.E. :
The inheritance pattern of factor XII (Hageman) deficiency in domestic cats. Can J Comp Med 44:309-14, 1980. Pubmed reference: 7427778.
1977 Green, R.A., White, F. :
Feline factor XII (Hageman) deficiency. Am J Vet Res 38:893-5, 1977. Pubmed reference: 879587.

Edit History


  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 07 May 2014
  • Changed by Frank Nicholas on 13 Apr 2017