Possibly relevant human trait(s) and/or gene(s) (MIM number): 603592

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2000

History: This disorder was first reported in cattle by Mizoguchi (1997).

Inheritance: Pedigree analysis by Watanabe et al. (2000) revealed autosomal recessive inheritance in Japanese Black cattle. Similar evidence was reported for Tyrolean Grey cattle by Murgiano et al. (2016).

Mapping: By conducting a genome scan on 21 affected offspring and their parents (21 dams and two sires), each genotyped with 200 microsatellites, Watanabe et al. (2000) linkage-mapped this disorder to the "centromeric region of bovine chromosome (BTA) 24". They then FISH-mapped the most likely comparative candidate gene (based on the most likely causative gene in humans), namely Drosophila ma-l orthologue (encoding the putative molybdopterin cofactor sulfurase, which is required for normal activity of both XDH and AO; see Clinical section), to "BTA24q13.1–13.3", which corresponds to the linkage-mapped location of the disorder locus.

Molecular basis: Cloning and sequencing of the bovine gene encoding molybdopterin cofactor sulfurase (MCSU, now called MOCOS) in normal and affected cattle, by Watanabe et al. (2000), revealed the causal mutation to be a 3bp deletion (c.769_771delTAC) of codon 257 (deleting Tyr) in the MOCOS gene.

Murgiano et al. (2016) discovered a different mutation in the MUCOS gene as the likely cause in Tyrolean Grey cattle: "1 bp deletion in the molybdenum cofactor sulfurase (MOCOS) gene (g.21222030delC; c.1881delG and c.1782delG), located in an 11 Mb region of homozygosity on BTA 24)".

Clinical features: As reported by Watanabe et al. (2000), this disorder is "characterized by elevated xanthine secretion in the urine associated with lethal growth retardation at approximately 6 months of age . . . Affected cattle had expanded renal tubules containing xanthine calculi ranging from 1–3 mm in diameter". A diagnostic feature is the lack of xanthine dehydrogenase (XDH) and aldehyde oxidase (AO).

Prevalence: Watanabe et al. (2000) "confirmed that more than 300 xanthinuria-affected [Japanese Black] cattle have been recorded over the last 20 years and that all parents were descendants of a putative founder sire. Affected male, female, and unknown offspring numbered 177, 148, and 9, respectively."

Breed: Japanese Black.

Associated gene: