Homozygous deletion in MOCOS gene is associated with nephrologic syndrome in Tyrolean Grey

Background Nephrologic syndromes have been extensively described in domestic animals. In a previous report we described kidney stones and kidney abnormalities in two Tyrolean Grey cattle twins. The young calves showed inexorable weight loss, skeletal abnormalities and delayed development. The initial diagnosis was of a form of Renal Dysplasia. Results Pedigree analysis revealed a common ancestor and we inferred a homozygous recessive mechanism of inheritance. We genotyped the cases and searched for extended regions of homozygosity to select suitable candidate regions. We sequenced the whole genome of a case and detected in a homozygous region a 1 bp deletion present in the 9th exon of the MOCOS gene. The MOCOS protein is responsible for Molybdenum Cofactor sulfation, and mutations in MOCOS has been associated with metabolic syndromes and Xanthinuria, a renal condition causing developmental problems and accumulation of kidney stones. The mutation was present in homozygosity only in the cases, and is present in heterozygosity in the family members and in roughly 3.5% of the Tyrolean Grey population tested. The mutation is predicted to be highly disruptive, creating a frameshift and premature stop codon. The predicted truncated mutant MOCOS protein would be roughly 30% shorter compared to the wild types. Conclusions We propose the mutation as causative of the renal syndrome and we suggest that the kidney stones and developmental abnormalities in the kidney and bones of the cases were related to an extremely severe form of Xanthinuria that had an early onset in utero.