Hämophilie A und B beim Hund

Mischke, R.

doi:10.1055/s-0038-1623619

Cited by 6 publications

(25 citation statements)

References 48 publications

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“…Inherited bleeding disorders encompass aberrations in primary hemostasis, coagulation, and fibrinolysis caused by genetic variants interfering directly or indirectly with platelet function. Hemophilia A is the most common coagulation factor disorder in dogs resulting from mutations in F8 gene [1,2]. Factor VIII (FVIII), one of the largest coagulation factors, consists of a heavy and a light chain.…”

Section: Introductionmentioning

confidence: 99%

A SINE Insertion in F8 Gene Leads to Severe Form of Hemophilia A in a Family of Rhodesian Ridgebacks

Kehl

Haaland

Langbein-Detsch

et al. 2021

Genes

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Hemophilia A is the most common coagulation factor disorder in humans and dogs. The disease is characterized by the lack or diminished activity of Factor VIII (FVIII), caused by variants in the F8 gene and inherited as an X chromosomal trait. Two related male Rhodesian Ridgebacks were diagnosed with Hemophilia A due to reduced FVIII activity. The purpose of the study was to determine the genetic cause and give breeding advice for the remaining family members in order to eradicate the variant. By Sanger sequencing a short interspersed nuclear element (SINE) insertion in exon 14 of the F8 gene was found. Perfect correlation of this genetic variant with clinical signs of hemophilia A in the family tree, and the lack of this genetic variant in more than 500 unrelated dogs of the same and other breeds, confirms the hypothesis of this SINE being the underlying genetic cause of Hemophilia A in this family. The identification of clinically unaffected female carriers allows subsequent exclusion of these animals from breeding, to avoid future production of clinically affected male offspring and more subclinical female carriers.

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Section: Introductionmentioning

confidence: 99%

A SINE Insertion in F8 Gene Leads to Severe Form of Hemophilia A in a Family of Rhodesian Ridgebacks

Kehl

Haaland

Langbein-Detsch

et al. 2021

Genes

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“…Spontaneous hemarthrosis, hematoma formation without known inciting causes, and increased bleeding after trauma and surgery are well-recognized complications of severe hemophilia in humans, dogs, and other mammalian species, leading to major morbidity and mortality [1,3,4]. Similarly, all affected male purebred Newfoundland and hybrid dogs in the family reported here exhibited severe hemorrhage, including mediastinal and subcutaneous hematomas, hemarthrosis, and gingival bleeding following loss of deciduous teeth.…”

Section: Discussionmentioning

confidence: 78%

“…Hemophilia A and B are X-linked recessively inherited coagulopathies that may cause severe bleeding in humans and domestic animals. The conditions are caused by mutations in the F8 or F9 gene, leading to reduced plasma activity of coagulation factor (F) VIII or IX, respectively [1][2][3][4][5][6]. Several F8 and F9 gene variants have been reported in bleeding dogs of various breeds [7][8][9][10][11][12][13] and are listed in the Online Mendelian Inheritance of Animals database (OMIA [14], Hemophilia A 000437-9615, and Hemophilia B 000438-9615).…”

Section: Introductionmentioning

confidence: 99%

A Single Base Insertion in F9 Causing Hemophilia B in a Family of Newfoundland–Parti Standard Poodle Hybrid Dogs

Kuder

Sandzhieva-Vuzzo²,

Kehl

et al. 2021

Genes

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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.

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“…Affected dogs, as in the present case, are usually males that are offspring of a female carrier. 15 In the presented cases, the non-sense variant led to a frameshift and alteration of the amino acid sequence terminating at position seven (p.Asn1069IlefsTer7), thereby causing mRNA non-sensemediated decay or the production of a shortened and probably non-functional FVIII protein without the light chain. The light chain encoded by exons 14-26 contains the C2 domain, which is essential for FVIII-vWF complex formation, enabling the circulation of FVIII in the bloodstream.…”

Section: Discussionmentioning

confidence: 88%

Hemophilia A in a litter of Border Collies caused by a one base pair deletion in the F8 gene

Brockmann,

Mensing,

von Luckner

et al. 2023

Veterinary Clinical Pathol

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In dogs, hemophilia A is known to affect different breeds. This is a case report describing hemophilia A in a litter of Border Collies. A privately owned bitch and her puppies (n = 7) were presented to the referring veterinarian after acute hematoma formation in the male offspring (n = 3) following microchip implantation. Global coagulation testing, as well as determination of factor VIII and IX activity, were carried out. Based on the results, factor VIII deficiency was suspected. Two of the affected male puppies were euthanized within a few days. Genetic testing of the mother and the surviving male puppy resulted in the description of a deletion in exon 14 of the F8 gene. This c.3206delA variant leads to a frameshift in amino acid sequence and a premature stop codon (p.Asn1069IlefsTer7). The detection of the mutation and consequent testing of related dogs revealed that the deletion most likely had occurred spontaneously in the mother and had been transmitted to several of her offspring in different litters. Identified carriers were taken out of the breeding scheme. It is concluded that genetic testing in the context of suspected genetic disease can lead to preventive measures, including timely exclusion of carriers from breeding.

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Hämophilie A und B beim Hund

Cited by 6 publications

References 48 publications

A SINE Insertion in F8 Gene Leads to Severe Form of Hemophilia A in a Family of Rhodesian Ridgebacks

A SINE Insertion in F8 Gene Leads to Severe Form of Hemophilia A in a Family of Rhodesian Ridgebacks

A Single Base Insertion in F9 Causing Hemophilia B in a Family of Newfoundland–Parti Standard Poodle Hybrid Dogs

Hemophilia A in a litter of Border Collies caused by a one base pair deletion in the F8 gene

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