Categories: Renal / urinary system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 220100 (trait) , 604144 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: 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 (Dog) (VBO_0200893).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: