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Familial nephropathy (FN) — Samoyed and English Springer Spaniel

Renal / urinario · Dog

Inherited nephropathy of juvenile onset with progressive glomerulonephritis due to alteration of the glomerular basement membrane (collagen IV). In the Samoyed it is caused by a mutation in COL4A5 (X-linked Alport syndrome); in the English Springer Spaniel the described form is autosomal recessive due to a mutation in COL4A4. It produces proteinuria and progression to renal failure in the young animal.
Inheritance patternSamoyed: X-linked recessive (COL4A5). English Springer Spaniel: autosomal recessive (COL4A4).
Gene / MutationSamoyed: COL4A5 c.3079G>T, p.(G1027*) (CanFam3.1 chrX:g.82196868G>T; OMIA:001112-9615). English Springer Spaniel: COL4A4 c.2713C>T, p.(Q905*) (CanFam3.1 chr25:g.39893376G>A; published as c.2806C>T p.(Q904*); OMIA:002618-9615).
PenetranceSamoyed: complete penetrance in hemizygous males; heterozygous females have variable involvement due to X inactivation (many healthy and some with late-onset disease). Springer: complete penetrance in homozygotes.
Codezjbp
Turnaround time15 days
Price52,60 €

Incidence

Samoyed: well-characterised X-linked form (Alport model). English Springer Spaniel: less frequent autosomal recessive form. No reliable carrier frequencies are published in large series.

Breeder management

- In the Samoyed, genotype females from affected lines before mating (COL4A5 variant)
- In the Samoyed, a carrier female must not be mated: mating with a clear male produces 50 % carrier daughters and 50 % affected hemizygous sons
- In the Springer, genotype breeding animals with the specific test and do not mate two carriers
- Affected males must not be used as breeding animals
- After a confirmed case, do not repeat the parental mating and communicate the status to the buyer

Specialist notes

Differential diagnosis with PLN of the SCWT/Airedale, familial amyloidosis and immune-mediated glomerulonephritis. Renal biopsy shows laminated glomerular basement membrane (Alport syndrome) in the Samoyed; in the Springer, the pattern is that of progressive glomerulonephritis. Determining the inheritance pattern (X-linked Samoyed versus autosomal Springer) is essential for genetic counselling.

References

1. Zheng K et al. (1994) Canine X chromosome-linked hereditary nephritis: a genetic model for human X-linked hereditary nephritis resulting from a single base mutation in the gene encoding the alpha 5 chain of collagen type IV. Proc Natl Acad Sci USA 91(9):3989-3993. PMID: 8171024
2. Nowend KL et al. (2012) Characterization of the genetic basis for autosomal recessive hereditary nephropathy in the English Springer Spaniel. J Vet Intern Med 26(2):294-301. PMID: 22369189
3. OMIA:001112-9615 (Nephritis, X-linked) y OMIA:002618-9615 (Nephropathy, COL4A4 related).

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