In other species: sheep

Categories: Renal / urinary system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 259900 (trait) , 604285 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0009823: primary hyperoxaluria type 1

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2012

Species-specific name: familial oxalate nephropathy

Molecular basis: Exon sequencing of the candidate gene AGXT in Coton du Tulear dogs by Vidgren et al. (2012) revealed a missense mutation to be the cause of this disorder; specifically "a single base change (c.996G>A) that changed one conserved residue (p.Gly102Ser)".

Clinical features: Tibetan Spaniels with type 1 primary hyperoxaluria usually present at a young age (from 5 weeks of age) with vomiting, diarrhoea, inappetence, weight loss, poor growth, depression, polydipsia (excessive thirst), polyuria (excessive production of urine) and may have anaemia (Jansen and Arnesen, 1990). The two affected Tibetian Spaniels were emaciated and anaemic at 7- and 9-weeks of age when they were euthanised (Jansen and Arnesen, 1990). Vidgren et al. (2012) report that in Coton de Tulear puppies onset is sudden, starting at an age of 3–4 weeks and resulted in euthanasia within a week. IT thanks DVM student Jess Hanna, who provided the basis of this contribution in May 2023

Pathology: Jansen and Arnesen (1990) report end-stage kidney lesions consistent with an oxalate nephropathy in two affected Tibetan Spaniels at 7- and 9-weeks of age. Vidgren et al. (2012) reported postmortem findings in seven affected Coton de Tulear puppies: "The only significant findings were in the kidneys, which were pale with pinpoint white foci scattered in the cortex. Numerous oxalate crystals ... were present in the tubules in the renal cortex and at the corticomedullary junction. Smaller crystals were present below the tubular epithelium. Uroliths or nephrocalcinosis were not present."

Breeds: Coton de Tulear (Dog) (VBO_0200389), Tibetan Spaniel (Dog) (VBO_0201352).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: