Hereditary factor XI (FXI) deficiency is characterized as an autosomal mild to moderate coagulopathy in humans and domestic animals. Coagulation testing revealed FXI deficiency in a core family of Maine Coon cats (MCCs) in the United States. Factor XI-deficient MCCs were homozygous for a guanine to adenine transition resulting in a methionine substitution for the highly conserved valine-516 in the FXI catalytic domain. Immunoblots detected FXI of normal size and quantity in plasmas of MCCs homozygous for V516M. Some FXI-deficient MCCs experienced excessive post-operative/traumatic bleeding. Screening of 263 MCCs in Europe revealed a mutant allele frequency of 0.232 (23.2%). However, V516M was not found among 100 cats of other breeds. Recombinant feline FXI-M516 (fFXI-M516) expressed ~4% of the activity of wild-type fFXI-V516 in plasma clotting assays. Furthermore, fFXIa-M516 cleaved the chromogenic substrate S-2366 with ~4.3-fold lower catalytic efficacy (k_cat/K_m) than fFXIa-V516, supporting a conformational alteration of the protease active site. The rate of FIX activation by fFXIa-M516 was reduced >3-fold compared with fFXIa-V516. The common missense variant FXI-V516M causes a cross-reactive material positive FXI deficiency in MCCs that is associated with mild-moderate bleeding tendencies. Given the prevalence of the variant in MCCs, genotyping is recommended prior to invasive procedures or breeding.

Liquid feed is susceptible to microbiological growth. Yeasts are said to cause sudden death in swine due to intestinal gas formation. As not all animals given high yeast content feed fall ill, growth and gas formation potential at body temperature were investigated as possible causally required properties. The best identification method for these environmental yeasts should be tested beforehand. Yeasts derived from liquid diets without (LD − S) and liquid diets with maize silage (LD + S) were examined biochemically (ID32C-test) and with MALDI-TOF with direct smear (DS) and an extraction method (EX). Growth temperature and gas-forming potential were measured. With MALDI-EX, most yeast isolates were identified: Candida krusei most often in LD − S, and C. lambica most often in LD + S, significantly more than in LD − S. Larger colonies, 58.75% of all yeast isolates, were formed at 25 °C rather than at 37 °C; 17.5% of all isolates did not grow at 37 °C at all. Most C. krusei isolates formed high gas amounts within 24 h, whereas none of the C. lambica, C. holmii and most other isolates did. The gas pressure formed by yeast isolates varied more than tenfold. Only a minority of the yeasts were able to produce gas at temperatures common in the pig gut.

Hemophilia B is an x-linked recessive hereditary coagulopathy that has been reported in various species. We describe a male Newfoundland–Parti Standard Poodle hybrid puppy and its family with hemophilia B from clinical manifestations to the molecular genetic defect. The index case presented for dyspnea was found to have a mediastinal hematoma, while surgical removal and transfusion support brought some relief, progressive hematoma formations led to humane euthanasia. Sequencing the F9 exons revealed a single nucleotide insertion resulting in a frameshift in the last exon (NM_001003323.2:c.821_822insA), predicted to result in a premature stop codon (NP_001003323.1:p.Asn274LysfsTer23) with a loss of 178 of 459 amino acids. The unexpected high residual plasma factor IX activity (3% to 11% of control) was likely erroneous, but no further studies were performed. Both the purebred Newfoundland dam and her sister were heterozygous for the insertion. Five additional male offspring developed severe hemorrhage and were hemizygous for the F9 variant and/or had a prolonged aPTT. In contrast, other male littermates had normal aPTTs and no evidence of bleeding. While they are related to a common Newfoundland granddam, the prevalence of the pathogenic variant in the Newfoundland breed is currently unknown. These clinical to molecular genetic studies illustrate that precision medicine is achievable in clinical companion animal practice.

Background Factor XI (FXI) deficiency is an autosomal recessive mild-moderate coagulopathy studied in humans, cattle, and dogs. Objective Characterization of clinical to genetic basis of FXI deficiency in Maine Coon cats (MCC), prevalence and effect of a F11 gene variant on the protein. Methods Coagulation testing revealed Factor XI deficiency in a MCC family with increased bleeding tendency. Exons of F11 were sequenced and compared to feline reference genomes. Studies of recombinant proteins were applied to assess the impact of the discovered gene variant. A TaqMan^®​ assay was established to screen MCC and other feline breeds. Results Affected MCC of both genders showed excessive, delayed post-operative, and gingival bleeding. Their aPTTs were prolonged, and FXI activities were markedly reduced. Sequencing of the 14 F11 exons of affected MCC revealed a single guanine to adenine exchange resulting in a methionine substitution for the highly conserved Val516. Immunoblot analysis detected normal size FXI protein in affected MCC, indicating the variant protein is produced and secreted. Conformational changes in the active site showed differences in the catalytic activity between wildtype and mutant FXIa. In clotting assays with human FXI deficient plasma, recombinant FXI-Met516 expressed only ~4% activity of wildtype FXI. Screening of 133 MCC revealed a 22.6% mutant allele frequency, but the variant was not present in 100 other cat breeds. Conclusion A common F11 missense variant in the catalytic domain causes FXI deficiency in MCC with mild-moderate bleeding tendencies. Genotyping of MCC is recommended to assess increased bleeding risk and selective breeding. Publication Date: 08 March 2022 (online) © 2022. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany