OMIA 002445-9615 : Xanthinuria, type I in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 607633 (gene) , 278300 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Probably Autosomal Recessive

Considered a defect: 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 (OMIA002445) 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.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
XDH xanthine dehydrogenase Canis lupus familiaris 17 NC_051821.1 (25524534..25464496) XDH Homologene, Ensembl, NCBI gene

Variants

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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1358 Mixed breed Xanthinuria, type I XDH splicing Naturally occurring variant CanFam3.1 17 g.24941551C>T c.654G>A p.(R189_L218del) ENSCAFT00000047701.2; Ensembl VEP reported variant as synonymous, splice region variant, cDNA sequencing revealed removal of all 93 bp of exon 8 (p.Arg189_Leu218del) . Genomic position based on supplementary table S3. (Tate et al., 2021) 2021 34584846

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2021 Tate, N.M., Minor, K.M., Lulich, J.P., Mickelson, J.R., Berent, A., Foster, J.D., Petersen, K.H., Furrow, E. :
Multiple variants in XDH and MOCOS underlie xanthine urolithiasis in dogs. Mol Genet Metab Rep 29:100792, 2021. Pubmed reference: 34584846. DOI: 10.1016/j.ymgmr.2021.100792.
2019 Jagannathan, V., Drögemüller, C., Leeb, T., Jagannathan, V., Drögemüller, C., Leeb, T. :
A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves. Anim Genet 50:695-704, 2019. Pubmed reference: 31486122. DOI: 10.1111/age.12834.
2016 Furrow, E., Tate, N., Minor, K., Mickelson, J., Peterson, K., Lulich, J. :
2016 ACVIM Forum Research Report Program: Three diverse mutations underlying canine xanthine urolithiasis. J Vet Intern Med 30:1537, 2016. DOI: 10.1111/jvim.13963.

Edit History


  • Created by Imke Tammen2 on 03 Oct 2021
  • Changed by Imke Tammen2 on 03 Oct 2021