OMIA 001819-9615 : Xanthinuria, type II in Canis lupus familiaris

In other species: cattle

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 603592 (trait) , 613274 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: 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).

Inheritance: Tate et al. (2021) conducted pedigree analysis in Manchester Terriers and their findings were consistent with autosomal recessive inheritance.

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 allele frequency of the MOCOS c.232G > T (p.Gly78Cys) variant was 0,13 and 0,10 in 386 Manchester Terriers and 285 English Toy Terriers, respectively. The allele frequency of the MOCOS c.383delC variant was 0.03 and 0 in 109 Cavalier King Charles Spaniels and 42 English Cocker Spaniels, respectively. The MOCOS c.137 T > C variant was absent from a population of 116 Dachshunds. (Tate et al., 2021)

Breeds: Cavalier King Charles Spaniel, Dachshund, English Cocker Spaniel, Manchester Terrier.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MOCOS molybdenum cofactor sulfurase Canis lupus familiaris 7 NC_051811.1 (53971999..53918314) MOCOS Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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
1356 Cavalier King Charles Spaniel English Cocker Spaniel Xanthinuria, type II MOCOS deletion, small (<=20) Naturally occurring variant CanFam3.1 7 g.53989863del c.383del p.(A128Gfs*30) c.383delC; transcript ENSCAFT00000028243.4; genomic position based on supplementary table S3 (Tate et al., 2021) 2021 34584846
1355 Manchester Terrier Xanthinuria, type II MOCOS splicing Naturally occurring variant CanFam3.1 7 g.53995018C>A c.232G>T p.(G48_Y77del) ENSCAFT00000028243.4; “Ensembl VEP determined the consequence of the variant to be a missense, splice region variant … the variant results in the removal of all 90 bp (30 amino acids) of exon 2 (p.Gly48_Tyr77del); the genomic position is based on supplementary table S3 (Tate et al., 2021)”; transcript ENSCAFT00000028243.4 2021 34584846
1357 Dachshund Xanthinuria, type II MOCOS missense Naturally occurring variant CanFam3.1 7 g.54001790A>G c.137T>C p.(L46P) transcript ENSCAFT00000028243.4; 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.
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.
2011 Gow, A.G., Fairbanks, L.D., Simpson, J.W., Jacinto, A.M., Ridyard, A.E. :
Xanthine urolithiasis in a Cavalier King Charles spaniel. Vet Rec 169:209, 2011. Pubmed reference: 21742684. DOI: 10.1136/vr.d3932.
1998 Flegel, T., Freistadt, R., Haider, W. :
Xanthine urolithiasis in a dachshund Veterinary Record 143:420-423, 1998. Pubmed reference: 9807792.
1997 Kucera, J., Bulkova, T., Rychla, R., Jahn, P. :
Bilateral xanthine nephrolithiasis in a dog Journal of Small Animal Practice 38:302-305, 1997. Pubmed reference: 9239633.
Vanzuilen, C.D., Nickel, R.F., Vandijk, T.H., Reijngoud, D.J. :
Xanthinuria in a family of Cavalier King Charles spaniels Veterinary Quarterly 19:172-174, 1997. Pubmed reference: 9413115.
1996 van Zuilen, C.D., Nickel, R.F., van Dijk, T.H., Reijngoud, D.J. :
Xanthinuria (xanthine oxidase deficiency) in two Cavalier King Charles spaniels Veterinary Quarterly 18:S 24-S 25, 1996.
1969 Delbarre, F., Holtzer, A., Auscher, C. :
[Xanthine urinary lithiasis and xanthinuria in a dachshund. Deficiency, probably genetic, of the xanthine oxidase system]. C R Acad Hebd Seances Acad Sci D 269:1449-52, 1969. Pubmed reference: 4982510.

Edit History


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