OMIA:001880-9615 : Cystinuria, type II - B in Canis lupus familiaris
Categories: Renal / urinary system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 220100 (trait) , 604144 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2013
Cross-species summary: The name of this entry has been created in line with the new expanded classification system for canine cystinuria suggested by Brons et al. (2013): "type I cystinuria when the disease shows autosomal recessive inheritance, type II when it shows autosomal dominant inheritance, and type III for sex-limited inheritance. . . . Involvement of the SLC3A1 gene is indicated by adding A, and similarly B indicates mutations in SLC7A9".
Inheritance: Brons et al. (2013) provided evidence consistent with autosomal dominant inheritance.
Molecular basis: Using the direct candidate gene strategy, based on clinical signs, Brons et al. (2013) identified "a single base missense mutation (c.964G>A) [in SLC7A9] changing the small hydrophobic glycine residue to the larger, charged basic amino acid arginine (p.Gly322Arg) in transmembrane domain 9 of the light subunit bo,+AT" as causal in Miniature Pinschers.
A SLC7A9 variant (c.649A>G; p.(A217T) has been identified by Harnevik et al. (2006) in English bulldogs, but there appears to be no support for the variant to be causal (Harnevik et al., 2006; Ruggerone et al., 2016; Fitzwilliams et al. 2023). It appears that all affected English bulldogs in these three studies were also homozygous for two likely causal SLC3A1 variants (p.(I192V) and p.(S698G) (see OMIA:000256-9615 : Cystinuria, type I - A in Canis lupus familiaris). The affected dogs were reported to be also either heterozygous or homozygous for the SLC7A9 variant (Harnevik et al., 2006; Ruggerone et al., 2016, Fitzwilliams et al. 2023), which according to Fitzwilliams et al. (2023) is a common allele in the breed (allele frequency for c.649A is 0.52 in English bulldogs from Denmark). The data presented by Fitzwilliams et al. (2023) showed that 10 out of 14 non cystinuric male dogs were heterozygous or homozygous for the A allele. Fitzwilliams et al. (2023) strongly recommend not to use "the variant in SLC7A9 as a test to predict the risk of developing cystinuria in male English bulldogs.”
Clinical features: As summarised by Brons et al. (2013), cystinuria type II - B is characterised by: occurs in males and females; not androgen-dependent; COLA [μmol/g creatinine (normal ≤500)] ≥ 700 in heterozygotes.
Breed: Miniature Pinscher.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|SLC7A9||solute carrier family 7 (amino acid transporter light chain, bo,+ system), member 9||Canis lupus familiaris||1||NC_051805.1 (119806922..119830085)||SLC7A9||Homologene, Ensembl , NCBI gene|
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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|
|85||Miniature Pinscher||Cystinuria, type II - B||SLC7A9||missense||Naturally occurring variant||CanFam3.1||1||g.119211938G>A||c.964G>A||p.(G322R)||NM_001048109.1; NP_001041574.1||2013||24001348||Genomic coordinates in CanFam3.1 provided by Robert Kuhn and Zoe Shmidt.|
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.
|2023||Fitzwilliams, T., Wolff-Sneedorff, J.L., Fredholm, M., Karlskov-Mortensen, P., Guldbrandtsen, B., Bruun, C.S. :|
|Evaluation of the value of genetic testing for cystinuria in the Danish population of English bulldogs. Anim Genet :, 2023. Pubmed reference: 36971195 . DOI: 10.1111/age.13321.|
|2021||Kovaříková, S., Maršálek, P., Vrbová, K. :|
|Cystinuria in dogs and cats: What do we know after almost 200 years? Animals (Basel) 11:2437, 2021. Pubmed reference: 34438894 . DOI: 10.3390/ani11082437.|
|2016||Ruggerone, B., Marelli, S.P., Scarpa, P., Polli, M. :|
|Genetic evaluation of English bulldogs with cystine uroliths. Vet Rec 179:174, 2016. Pubmed reference: 27388977 . DOI: 10.1136/vr.103615.|
|2015||Bartges, J.W., Callens, A.J. :|
|Urolithiasis. Vet Clin North Am Small Anim Pract 45:747-68, 2015. Pubmed reference: 26002797 . DOI: 10.1016/j.cvsm.2015.03.001.|
|2013||Brons, A.K., Henthorn, P.S., Raj, K., Fitzgerald, C.A., Liu, J., Sewell, A.C., Giger, U. :|
|SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria: a new classification system. J Vet Intern Med 27:1400-8, 2013. Pubmed reference: 24001348 . DOI: 10.1111/jvim.12176.|
|2006||Harnevik, L., Hoppe, A., Söderkvist, P. :|
|SLC7A9 cDNA cloning and mutational analysis of SLC3A1 and SLC7A9 in canine cystinuria. Mamm Genome 17:769-76, 2006. Pubmed reference: 16845473 . DOI: 10.1007/s00335-005-0146-4.|
- Created by Frank Nicholas on 06 Sep 2013
- Changed by Frank Nicholas on 06 Sep 2013
- Changed by Imke Tammen2 on 29 Mar 2023