Haemophilia A (factor VIII deficiency)

Breed

 Havanese Dogs

Disease

Haemophilia A is one of the most important inherited disorders of haemostasis in Havanese Dogs. The underlying pathomechanism of  Haemophilia A is a lack or decreased activity of factor VIII that plays a critical role in the coagulation cascade. Affected dogs present with hemorrhage that can vary from mild to severe depending on the degree of the disease. The clinical signs include haematomas of large sizes, bleeding of the nose, skin, muscles and joints. If the disease is severe and no precautions are taken, affected dogs can bleed to death after surgery or injuries.

Mutation and Mode of Inheritance

In cooperation with Prof. Dr. Mischke (Tierärztliche Hochschule Hannover) LABOKLIN was able to identify a SINE insert in exon 14 of the factor VIII gene that is responsible for the lack of active factor VIII protein in Havanese Dogs.
 
Haemophilia A is a sex-linked disorder (x-chromosomal recessive). Male dogs express the disease when they have one mutated x-chromosome. The mutated x-chromosome comes from the bitch. In most cases female dogs are carrier of one mutated x-chromosome without being diseased (conductor). According to Mendel's Law of Inheritance, 50% of the male puppies of a carrier bitch will have the mutated x-chromosome and express the disease and 50% of the female puppies will be healthy carriers (conductors). Female dogs will be diseased when they have two mutated x-chromosomes (one from the mother, one from the father). In that case both, father and mother must have the mutated x-chromosome (e.g. diseased male dog  bred to conductor bitch).

There are 3 possible genotypes:
 
1. Homozygous healthy:
Genotype female: N(X)/N(X),
Genotype male: N(X)/Y (homozygous healthy)
A dog like this is healthy and does not carry the mutated x-chromosome. Offspring of this dog will not get the mutated x-chromosome.
 
2. Heterozygous carrier (only female):
Genotype female: N(X)/FVIII(X) (heterozygous carrier)
A bitch like this carries one copy of the mutated gene. It is unlikely that the bitch will suffer from haemophilia A, however there is a 50% chance that she will pass on the mutation to her offspring.
 
3. Homozygous affected:
Genotype female FVIII(X)/FVIII(X) (homozygous affected)
Genotype male FVIII(X)/Y (hemizygous affected)
Because of the x-chromosomal mode of inheritance, a homozygous affected female dog carries two mutated x-chromosomes and a hemizygous affected male dog carries one mutated x-chromosome. Female and male affected dogs have a high risk to express haemophilia A. The bitch will pass on the mutation to a 100% of her offspring and 50% of the offspring of the male dog will get the mutated x-chromosome.

The DNA Test

The mutation responsible for haemophilia A can now be identified using our DNA-test. The test can be performed on dogs of any age and even puppies can be tested. The DNA test does not only differentiate healthy and diseased dogs, but furthermore identifies healthy carrier (female) dogs. This is of crucial importance for dog breeders. 
To achieve a maximum reliability of the test result, we perform the DNA-test of each submitted sample in two independent test runs.

Sample Material

Sample material for the test is 1 ml of EDTA blood or a buccal swab. You can request swab kits and a detailed protocol free of charge at Laboklin.

Duration

 Usually you will receive the test result 3-5 working days after receival of your sample

For further information please contact

Dr. Petra Kühnlein or Dr. Ines Langbein-Detsch
LABOKLIN GmbH & Co.KG
Steubenstraße 4
D-97688 Bad Kissingen /german

Phone: +49-971-72020 /72020 or Fax: +49-971 / 7202995
Email: labogenlaboklin.de