Test Detail

Multi-disease panel for the German Shorthaired Pointer that groups four molecular tests for hereditary conditions described in the breed: von Willebrand disease type 2 (VWF), junctional epidermolysis bullosa (LAMA3), exfoliative cutaneous lupus erythematosus (UNC93B1) and acral mutilation syndrome (GDNF-AS). It allows management of coagulopathies, blistering dermatoses, cutaneous autoimmunity and sensory neuropathies.

Applicable breed: German Shorthaired Pointer. vWD2 is documented in German Shorthaired and Wirehaired Pointers (OMIA:001339-9615). JEB is described in German Pointer (OMIA:001677-9615), with prevalence and genetic trend studies in Italian populations (Pertica et al., 2010; Frattini et al., 2021). ECLE is described in German Shorthaired Pointer and Vizsla (OMIA:001609-9615). AMS is validated in German Shorthaired Pointer among other breeds (OMIA:001514-9615). No reliable carrier frequencies are published for the four variants (limited data).

- Mucocutaneous bleeding and prolonged bleeding after surgery or trauma (vWD2)\n- Blisters and cutaneous-mucosal detachment with neonatal onset, oral ulcers and onychomadesis (JEB)\n- Generalized scaling, erythema and crusts, with onychomadesis and chronic course (ECLE)\n- Painless ulcers and mutilations on digits and paw pads, with loss of distal nociception and preserved proprioception (AMS)

The panel tests were developed independently. vWD2 in the Pointer was associated with VWF variants: c.4937A>G (p.N1646S) in the shorthaired (Kramer et al., 2004) and c.1657T>G (p.W553G) in the wirehaired, which also segregates in the shorthaired (Vos-Loohuis et al., 2017). JEB was described in the Pointer as a natural animal model of human JEB, caused by a 6.5 kb satellite DNA insertion in intron 35 of LAMA3 (Capt et al., 2005). ECLE was mapped to CFA18 (Wang et al., 2011) and in 2020 the causal variant was identified in UNC93B1 (Leeb et al., 2020). AMS was associated with a point mutation in the lincRNA GDNF-AS (Plassais et al., 2016).

- Genotype breeding animals before mating\n- Recessive conditions (JEB, ECLE, AMS) and, depending on lineage, vWD2: do not mate carrier×carrier (25 % affected homozygotes); carrier×clear produces 0 % affected and 50 % carriers\n- Given the severity and the absence of curative treatment for JEB, do not mate known carriers in at-risk lines\n- For vWD2, prioritize breeders clear of the variant involved in the breed and consult the veterinarian before deciding the mating\n- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer

vWD2 is confirmed by antigen and VWF activity assays; assess bleeding time before surgery in non-genotyped animals. JEB requires biopsy with immunofluorescence/electron microscopy (separation at the lamina lucida) and variant-specific genetic confirmation for the Pointer. ECLE requires biopsy with interface dermatitis and immunohistochemistry, and immunomodulatory management. AMS requires neurological assessment (loss of nociception with preserved proprioception) and exclusion of other causes of painless ulcers. Check which specific variants each laboratory includes.

1. Kramer JW et al. 2004. A von Willebrand's factor genomic nucleotide variant and polymerase chain reaction diagnostic test associated with inheritable type-2 von Willebrand's disease in a line of German Shorthaired Pointer dogs. Vet Pathol 41(3). PMID 15133170.
2. Vos-Loohuis M et al. 2017. A novel VWF variant associated with type 2 von Willebrand disease in German Wirehaired Pointers and German Shorthaired Pointers. Anim Genet 48(4). PMID 28696025.
3. Capt A et al. 2005. Inherited junctional epidermolysis bullosa in the German Pointer: establishment of a large animal model. J Invest Dermatol 124(3). PMID 15737193.
4. Pertica G et al. 2010. Prevalence of inherited junctional epidermolysis bullosa in German shorthaired pointers bred in Italy. Vet Rec 167(19). PMID 21257512.
5. Frattini S et al. 2021. Genetic trend of the junctional epidermolysis bullosa in the German shorthaired pointer in Italy. Vet Rec Open 8(1). PMID 34457315.
6. Wang P et al. 2011. Familial cutaneous lupus erythematosus (CLE) in the German shorthaired pointer maps to CFA18, a canine orthologue to human CLE. Immunogenetics 63(4). PMID 21132284.
7. Leeb T et al. 2020. A Missense Variant Affecting the C-Terminal Tail of UNC93B1 in Dogs with Exfoliative Cutaneous Lupus Erythematosus (ECLE). Genes (Basel) 11(2). PMID 32028618.
8. Plassais J et al. 2016. A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies. PLoS Genet 12(12). PMID 28033318.
9. Paradis M et al. 2005. Acral mutilation and analgesia in 13 French spaniels. Vet Dermatol 16(2). PMID 15842538.
10. Correard S et al. 2019. Canine neuropathies: powerful spontaneous models for human hereditary sensory neuropathies. Hum Genet 138(5). PMID 30955094.
11. Bardagí M et al. 2011. Acral mutilation syndrome in a miniature pinscher. J Comp Pathol 144(2-3). PMID 20961556.
12. OMIA:001339-9615 (Von Willebrand disease II), OMIA:001677-9615 (Epidermolysis bullosa junctionalis, LAMA3-related), OMIA:001609-9615 (Exfoliative cutaneous lupus erythematosus), OMIA:001514-9615 (Acral mutilation syndrome).