Hemophilia in Canis familiaris (dogs)

General information MIM number: MIM number: MIA number: MIA number:

What is hemophilia? Hemophilia is a bleeding disorder of varying severity that is due to a deficiency in specific clotting factors. Hemophilia is a bleeding disorder of varying severity that is due to a deficiency in specific clotting factors. It is an X-linked, recessive disorder which is one of the few sex-linked traits in dogs. It is an X-linked, recessive disorder which is one of the few sex-linked traits in dogs.X-linked, recessive disorderX-linked, recessive disorder Hemophilia found in dogs are very closely related to the hemophilia found in humans. Hemophilia found in dogs are very closely related to the hemophilia found in humans.

Chromosomes present in a female dog Sex chromosomes

There are two major types of hemophilia: There are two major types of hemophilia:  Hemophilia A is defective in coagulation factor VIII and is sometimes called royal hemophilia because it occurred in descendants of Queen Victoria.  Hemophilia B is defective in coagulation factor IX and is also known as Christmas disease because it was first observed in a patient named Stephen Christmas. Both hemophilia types are X-linked disorders but however differentiated because it occurs on different genes on the X chromosome. Both hemophilia types are X-linked disorders but however differentiated because it occurs on different genes on the X chromosome.

History Queen Victoria

Molecular Genetics of hemophilia The molecular basis of hemophilia B are mutations in the F9 gene. The molecular basis of hemophilia B are mutations in the F9 gene. This genetic disorder is caused by many different types of mutations such as: This genetic disorder is caused by many different types of mutations such as:  Deletions  Insertions  Point mutations  Duplications  Inversions

Because males have only 1 X chromosome, a male dog is either affected or clear of the defect. Because males have only 1 X chromosome, a male dog is either affected or clear of the defect. Females, with 2 X chromosomes, may be affected (abnormal gene on both chromosomes), clear, or a carrier with no clinical signs (one gene affected). Females, with 2 X chromosomes, may be affected (abnormal gene on both chromosomes), clear, or a carrier with no clinical signs (one gene affected). In effect, the disease is carried by females but affects mostly males. In effect, the disease is carried by females but affects mostly males.

Factor IX Cytogenetic Location: Xq27.1- q27.2 Cytogenetic Location: Xq27.1- q27.2 The factor IX gene is about 34kb long. The factor IX gene is about 34kb long. Encompasses 8 exons and 7 introns. Encompasses 8 exons and 7 introns. Encodes a protein that consists of 415 amino acids Encodes a protein that consists of 415 amino acids And has a molecular weight of D And has a molecular weight of D F9 gene

How does hemophilia work?

Clotting Cascade Factor XII

Bull TerrierLhasa Apso Airedale TerrierLabrador Types of dogs affected

Clinical signs of hemophilia B Symptoms vary widely, based on the severity of the bleeding disorder bloody diarrhea bloody diarrhea bleeding under the skin bleeding under the skin lameness lameness

Clinical signs of hemophilia B Where hemophilia is more severe, you may see signs of a problem at a fairly early age Pups may have prolonged bleeding associated with the loss of baby teeth. Pups may have prolonged bleeding associated with the loss of baby teeth. Bleeding under the skin Bleeding under the skin Bleeding into muscles or joints will often cause lameness. Bleeding into muscles or joints will often cause lameness. Unfortunately, dogs with severe hemophilia often die or are euthanized because of recurrent or uncontrollable bleeding problems. Unfortunately, dogs with severe hemophilia often die or are euthanized because of recurrent or uncontrollable bleeding problems.

Detection of hemophilia Diagnosis is made through blood tests to determine:   Blood clotting   Level of clotting factors   Missing clotting factors

How is hemophilia treated? There is no cure for this disorder. Periodic transfusions Periodic transfusions Administer fresh plasma, fresh frozen plasma, or cryosupernatant (factor IX) plasma. Administer fresh plasma, fresh frozen plasma, or cryosupernatant (factor IX) plasma.

Gene Therapy