Genetic panel for the American Bully grouping five recessive hereditary conditions prevalent in bull/pit-type breeds: crd1-type progressive retinal atrophy (crd1-PRA, early photoreceptor degeneration), cystinuria (cystine stones in the urinary tract), hyperuricosuria/hyperuricaemia (HUU, risk of urate uroliths), neuronal ceroid lipofuscinosis (NCL, neurodegenerative degeneration of adult onset) and degenerative myelopathy (DM, exon 2 variant of SOD1). The American Bully descends from the American Staffordshire Terrier and shares several variants through a founder effect.

American Bully (and related pit/bull-type breeds). ARSG-related NCL is characterised in AmStaff/APBT (allele at 3.4 % in AmStaff, Donner 2023 n>1M); it is assumed to be shared with the American Bully by ancestry, with no published cases in the breed. For crd1-PRA, HUU and cystinuria in the American Bully, population figures are not reliably published (limited data).

- crd1-PRA: night blindness and progressive visual loss from several months of age; fundus changes\n- Cystinuria: cystine urolithiasis, obstructive or recurrent, mainly in males\n- HUU: urate uroliths in the urinary tract, obstructive, in males\n- NCL: adult onset with ataxia, mental-motor deterioration, myoclonus and cerebellar signs\n- DM: paresis/ataxia of the pelvic limbs in adults, progression to paraplegia

crd1-PRA was described in the American Staffordshire Terrier by Kijas et al. (2004) and characterised by Goldstein and colleagues (2013) as a 3-bp deletion in exon 21 of PDE6B (c.2407_2409del, p.(803del)). Adult-onset NCL was associated with a missense variant of ARSG (c.296G>A, p.R99H) by Abitbol and colleagues (2010), a form documented in the American Staffordshire Terrier and assumed in the American Bully by ancestry. Cystinuria of the bull/mastiff stock (English and French Bulldog) is due to the haplotype of two SLC3A1 variants c.[574A>G;2092A>G] (Brons et al., 2013); its clinical validation in the American Bully is limited. HUU is associated with the classic SLC2A9 variant and DM with the exon 2 variant of SOD1, present in many breeds.

- Genotype breeding animals for PDE6B, SLC2A9, ARSG, SOD1 exon 2 and the cystinuria variant before mating\n- Do not cross two carriers for the same variant\n- A carrier may be crossed with a clear animal and the offspring intended for breeding must be tested\n- After a confirmed case, do not repeat the parental cross and communicate the status to the buyer\n- For HUU and cystinuria, recommend diet and management (low purine, low methionine) even if the test is positive, and urinary monitoring\n- Remember that DM has incomplete penetrance: not all SOD1 homozygotes develop disease

crd1-PRA must be distinguished from other PRAs (prcd-PRA, etc.); the crd1 test does not exclude other forms. ARSG-related NCL has an adult presentation and must be differentiated from other degenerative ataxias. Cystinuria and HUU share a clinical presentation (urolithiasis) and require stone analysis. DM is only attributable to SOD1 after ruling out spinal cord compression (MRI, myelography).

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OMIA001674-9615 / OMIA000256-9615 / OMIA001033-9615 / OMIA001503-9615 / OMIA000263-9615.