Multi-disease genetic panel for the English Cocker Spaniel combining three molecular tests: progressive retinal atrophy (prcd-PRA), familial nephropathy (FN) and acral mutilation syndrome (AMS). All three conditions have a characterised molecular basis and a recessive inheritance pattern. The panel is complementary to ocular examination and renal and neurological follow-up in breeding selection.

Applicable breed: English Cocker Spaniel. The PRCD and COL4A4 variants are present in breeding lines; AMS has low case numbers in the breed. Reliable carrier frequencies in the breeding population are not systematically published (limited data).

- Reduced night vision and progressive retinal atrophy (prcd-PRA)\n- Progressive blindness with altered fundus\n- Polydipsia, polyuria, weight loss and proteinuria from a young age (FN)\n- Progressive renal failure with uraemia (FN)\n- Biting and self-injury of the limbs without apparent cause (AMS)\n- Analgesia and loss of distal pain sensitivity (AMS)

Canine prcd-PRA was associated with the PRCD gene and its molecular test became widespread in multiple breeds. Familial nephropathy of the English Cocker Spaniel was characterised as a hereditary glomerulopathy due to a collagen IV defect (COL4A4) and a model of human Alport basement membrane nephropathy. Acral mutilation syndrome has been described in the English Cocker Spaniel and the English Springer Spaniel as a hereditary sensory neuropathy with self-mutilation; the GDNF variant was associated with pain insensitivity in sample breeds (Plassais 2016).

- Genotype breeding animals before mating; the panel covers three conditions in a single sample\n- For all three conditions (recessive): do not mate two carriers — 25% risk of affected homozygotes; carrier×clear is safe for offspring intended for breeding if tested\n- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer

prcd-PRA is confirmed by ocular examination and molecular testing; annual examination (ECVO/CERF) is complementary. Familial nephropathy is confirmed by renal biopsy (thickening and lamination of the glomerular basement membrane due to collagen IV) and molecular testing; the differential diagnosis includes other glomerulopathies and chronic pyelonephritis. AMS is a diagnosis of exclusion: rule out peripheral neuropathic pain, radicular lesion, arthritis and behavioural causes of self-injury before attributing the picture to the genetic variant.

1. Zangerl B et al. 2006, PRCD y prcd-PRA canina (PMID 16938425)
2. Davidson MG et al. 2007, nefropatía hereditaria autosómica recesiva del Cocker inglés por COL4A4 (PMID 17552442)
3. Andrade et al. 2020, frecuencia del alelo COL4A4 en Cockers ingleses (PMID 32734115)
4. Plassais J et al. 2016, mutación puntual en lincRNA junto a GDNF asociada a insensibilidad al dolor canina (PMID 28033318)
5. OMIA:002618 Nefropatía (COL4A4)