In other species: domestic cat

Categories: Renal / urinary system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 607633 (gene) , 278300 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2021

Cross-species summary: Animals with hereditary xanthinuria (excretion of large amounts of xanthine in the urine) may be asymptomatic, may have subclinical uroliths (xanthine stones), or present with clinical signs of urolithiasis. Urolith formation can be influenced by other biologic and environmental factors such as sex, diet and urine properties. Xanthinuria, type I (OMIA:002445) is caused by variation in the XDH gene and xanthinuria, type II (OMIA:001819) is caused by variation in the MOCOS gene. Information relating to xanthinuria without identified causal variants is listed under xanthinuria, generic (OMIA:001283).

Molecular basis: Furrow et al. (2016) reported in a conference abstract the identification of three likely disease-causing mutations for xanthine urolithiasis. Affected Cavalier King Charles Spaniels had a mutation resulting in a premature stop codon in the molybdenum cofactor sulfurase gene (MOCOS), affected Toy Manchester Terriers had a splice site mutation in MOCOS, and an affected mixed breed dog had a splice site mutation in the xanthine dehydrogenase (XDH) gene. These findings were included in the publication by Tate et al. (2021). Tate et al. (2021): "The aim of this study was to uncover variants underlying risk for xanthinuria in dogs. Affected dogs included two Manchester Terriers, three Cavalier King Charles Spaniels, an English Cocker Spaniel, a Dachshund, and a mixed-breed dog. ...Sanger sequencing of [candidate genes] XDH and MOCOS identified four putative causal variants ... : an XDH c.654G > A splice site variant that results in skipping of exon 8 (mixed-breed dog), a MOCOS c.232G > T splice site variant that results in skipping of exon 2 (Manchester Terriers), a MOCOS p.Leu46Pro missense variant (Dachshund), and a MOCOS p.Ala128Glyfs*30 frameshift variant that results in a premature stop codon (Cavalier King Charles Spaniels and English Cocker Spaniel). ... All variants were found in a homozygous state in the affected dogs, consistent with an autosomal recessive mode of inheritance."

Prevalence: The c.654G>A variant was not present in 813 dog sequences included in the Dog Biomedical Variant Database Consortium (Jagannathan et al., 2019).

Breed: Mixed Breed (Dog) (VBO_0200902).
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: