Genetic panel for the American Staffordshire terrier combining four recessive variants: crd1-type progressive retinal atrophy (crd1-PRA, early photoreceptor degeneration due to PDE6B), adult-onset neuronal ceroid lipofuscinosis (NCL due to ARSG), degenerative myelopathy (DM, exon 2 variant of SOD1) and the coat colour dilution locus D-locus d1 (changes eumelanin to diluted blue/fawn in homozygosity). The first three are diseases; the fourth is a coat characteristic.

American Staffordshire terrier. NCL due to ARSG: allele at ~3.4% in the AmStaff (Donner et al., 2023, n>1M), with clinical cases described in the breed. For crd1-PRA and DM, population frequencies are not reliably published (limited data). The MLPH d1 dilution variant is present at variable frequency.

- crd1-PRA: night blindness and progressive visual loss from several months of age; fundus changes
- NCL: adult onset with ataxia, mental-motor deterioration, myoclonus and cerebellar signs; cerebellar atrophy on MRI
- DM: paresis/ataxia of the pelvic limbs in adults, progression to paraplegia
- D-locus d1: in homozygosity, diluted coat tone (blue/fawn); no associated clinical signs (coat phenotype only)

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 in the American Staffordshire was associated with a missense variant in ARSG (c.296G>A, p.R99H) by Abitbol and colleagues (2010); its allele frequency in the breed has been estimated at around 3.4% (Donner et al., 2023, n>1M). DM exon 2 of SOD1 is pan-breed. The D-locus d1 (dilution) is associated with the classic MLPH variant (c.-22G>A).

- Genotype breeding animals for PDE6B, ARSG, SOD1 exon 2 and MLPH (d1) before mating
- For diseases: do not mate two carriers of the same variant
- For D-locus d1: the choice of diluted/non-diluted matings is an aesthetic criterion, but the buyer should be advised of the status
- A carrier may be mated to a clear animal and the offspring intended for breeding must be tested
- After a confirmed disease case, do not repeat the parental mating and inform the buyer of the status
- DM has incomplete penetrance: homozygous SOD1 status does not necessarily imply clinical development

crd1-PRA must be distinguished from other PRAs (the crd1 test does not exclude other forms). NCL due to ARSG has an adult presentation and must be differentiated from other degenerative ataxias; in recent studies the condition is partly reclassified as mucopolysaccharidosis. DM is only attributable to SOD1 after ruling out spinal cord compression. D-locus d1 in homozygosity may be associated in some breeds with colour dilution alopecia, but not systematically; the American Staffordshire may show a healthy coat in diluted animals.

1. Kijas JW et al. (2004). Cloning of the canine ABCA4 gene and evaluation in canine cone-rod dystrophies and progressive retinal atrophies. Mol Vis 10:223-232. PMID: 15064680
2. Goldstein O et al. (2013). IQCB1 and PDE6B mutations cause similar early onset retinal degenerations in two closely related terrier dog breeds. Invest Ophthalmol Vis Sci 54:7005-19. PMID: 24045995
3. Abitbol M et al. (2010). A canine arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis. Proc Natl Acad Sci USA 107:14775-80. PMID: 20679209
4. Donner J et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLoS Genet. PMID: 36848397
5. Awano T et al. (2009). Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy. Proc Natl Acad Sci USA. PMID: 19188595
6. Drögemüller C et al. (2007). A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs. J Hered. PMID: 17519392
OMIA001674-9615 / OMIA001503-9615 / OMIA000263-9615 / OMIA000031-9615.