Bernard-Soulier syndrome in Cocker Spaniel dogs: an Italian-Swiss research collaboration discovered the causative gene mutation for this fatal bleeding disorder
An international collaborative research group made up of researchers from the University of Bologna, the University of Bern (Switzerland), Clinica Veterinaria San Marco of Padova and Genefast has reported cases of an inherited coagulopathy in Cocker Spaniel dogs. The causative mutation for this genetic disease called Bernard-Soulier syndrome (BSS), has been discovered, and a direct gene test has been developed.
The disease causing mutation follows an autosomal recessive mode of inheritance. Only those dogs carrying two copies of the BSS mutation develop the hemorrhagic disease (see skills in pills).Those dogs who are carriers of a single copy of the mutation in heterozygous state (i.e. they have one copy of the mutant BSS allele and one copy of the normal wild-type allele) are completely healthy. These carrier dogs transmit the BSS mutation to 50%of their offspring. Having only one heterozygous BSS carrier parent, with one BSS clear (homozygous wild-type) parent, will ensure that no BSS-affected offspring will be born.
To be able to identify both the affected and the carrier dogs, and to guide the breeding programs, reliable genetic testing, BSS1st VetTest™, has been set up and is available worldwide exclusively at Genefast. The BSS1st VetTest™ identifies dogs with the mutation in a homozygous state (BSS1st /BSS1st), carrier dogs (BSS1st /wt) and dogs carrying only the wild-type allele (wt/wt). The genetic test is pivotal in reaching a correct diagnosis in the case of hemorrhagic episodes in order to effectively manage the hemorrhagic diathesis, using the correct therapeutic options. The BSS1st VetTest™ genetic test may also be used in breeding to plan reproduction so as to avoid the birth of affected dogs and the diffusion of the mutated allele in the breed.
The BSS1st VetTest™ results are as follows:
BSS1st -2 affected dogs, homozygous for the mutation
BSS1st -1 carrier dog, heterozygous
BSS1st -0 free (clear) dogs, homozygous wild-type
This is the first report of BSS in domestic animals, in particular in Cocker Spaniel dogs.
Skills in pills:
Bernard-Soulier syndrome (BSS): BSS is an autosomic recessive hereditary bleeding diatesis. The disease is considered a rare disease due to its relatively low frequency in humans but it is also included in the orphan disease list since it is frequently overlooked or misdiagnosed.
BSS is caused by a defective platelet membrane receptor which binds the von Willebrand factor (vWF). At vascular injury sites, the link between the platelet membrane receptor and the vWF stabilizes the platelet plug. In affected subjects, the thrombus is unstable and ineffective. In men, many mutations have been discovered, each causing slightly different BSS variants with different severity. No evidence of BSS in animals had previously been reported.
From a clinical standpoint, BSS is typically characterized by a lower than normal platelet count. Furthermore, platelets show an increased average size; hence, they are called “giant platelets”. However, the platelets have an inherent defect which prevents plug formation leading to a bleeding tendency. In humans, the clinical signs are usually mild and include mucosal bleeding, purpuric skin bleeding, epistaxis, menorrhagia, and buccal and gastrointestinal bleeding. In dogs, the clinical signs are frequently severe, characterized by mucosal bleeding with unresponsive nose bleeding, melena and urinary bleeding, and are frequent owner complaints. In certain situations, such as delivery or in cases of traumatic events or surgery, BSS may represent a life-threatening condition. Laboratory exams may reveal a mild thrombocytopenia with “giant platelets” (increased Mean Platelet Volume, MPV). These findings are common and are not specific of BSS. Hence, BSS may easily be misdiagnosed with other platelet disorders, such as idiopathic or secondary immuno-mediated thrombocytopenia(IMT). Typically, IMT requires the prompt administration of immunosuppressive drugs which are evidently useless or even harmful in BSS-affected dogs. In turn, BSS may benefit from early treatment with platelet concentrates or whole blood transfusions.
How to test a dog
Before sampling, the BSS1st VetTest™ form should be completed
Identify the tubes with the same ID as reported in the BSS1st VetTest™ form
The preferred samples for the BSS1st VetTest™ are the following:
- blood sample collected in EDTA tube
- 2 buccal swabs or 2 buccal brushes put into a container WITHOUT medium. If two-headed cotton swabs are used, please cut off the unused head. The presence of faint red hematic colour guarantees that enough DNA has been collected.
Recommendations for swabs or cytobrushes: When swabs or cytobrushes are used, the dogs need to be kept isolated from other dogs for at least 12 hours and must fast for 4 hours.Carefully avoid any contact of the swab/cytobrush with other swabs/cytobrushes.
Seal the blood tubes or the swab tubes using parafilm
Put the tubes into a closed sealable envelope wrapped in cellulose paper. Put the envelope in a Sealed Air Bubble airmail envelope.
Keep the sample refrigerated at +2 -+6°C until shipped
Ship using express courier or ordinary mail to:
Via Jolanda Baldassari 6
47122 FORLI’ (FC)
Price List and Method of payment:
The cost of analysis is 67,10 euro
The method of payment is money transfer to the following bank address:
Swift code BPMOIT22XXX; IBAN code IT59X0538766700000001190065
Please, take care that the bank fee will not divided but entirely sustained by you.