This study was performed at the School of Veterinary Medicine, University of Pennsylvania, in part as fulfillment of the doctoral thesis work of the first author Ann-Kathrin Brons at the University of Zürich, Switzerland
SLC3A1 and SLC7A9 Mutations in Autosomal Recessive or Dominant Canine Cystinuria: A New Classification System
Article first published online: 3 SEP 2013
Copyright © 2013 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 27, Issue 6, pages 1400–1408, November/December 2013
How to Cite
Brons, A.-K., Henthorn, P.S., Raj, K., Fitzgerald, C.A., Liu, J., Sewell, A.C. and Giger, U. (2013), SLC3A1 and SLC7A9 Mutations in Autosomal Recessive or Dominant Canine Cystinuria: A New Classification System. Journal of Veterinary Internal Medicine, 27: 1400–1408. doi: 10.1111/jvim.12176
- Issue published online: 13 NOV 2013
- Article first published online: 3 SEP 2013
- Manuscript Accepted: 24 JUL 2013
- Manuscript Revised: 11 JUL 2013
- Manuscript Received: 9 APR 2013
- AKC Canine Health Foundation
- NIH. Grant Number: OD 010939
- Hereditary disease;
- Metabolic disease;
Cystinuria, one of the first recognized inborn errors of metabolism, has been reported in many dog breeds.
To determine urinary cystine concentrations, inheritance, and mutations in the SLC3A1 and SLC7A9 genes associated with cystinuria in 3 breeds.
Mixed and purebred Labrador Retrievers (n = 6), Australian Cattle Dogs (6), Miniature Pinschers (4), and 1 mixed breed dog with cystine urolithiasis, relatives and control dogs.
Urinary cystinuria and aminoaciduria was assessed and exons of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA.
In each breed, male and female dogs, independent of neuter status, were found to form calculi. A frameshift mutation in SLC3A1 (c.350delG) resulting in a premature stop codon was identified in autosomal-recessive (AR) cystinuria in Labrador Retrievers and mixed breed dogs. A 6 bp deletion (c.1095_1100del) removing 2 threonines in SLC3A1 was found in autosomal-dominant (AD) cystinuria with a more severe phenotype in homozygous than in heterozygous Australian Cattle Dogs. A missense mutation in SLC7A9 (c.964G>A) was discovered in AD cystinuria in Miniature Pinschers with only heterozygous affected dogs observed to date. Breed-specific DNA tests were developed, but the prevalence of each mutation remains unknown.
Conclusions and clinical importance
These studies describe the first AD inheritance and the first putative SLC7A9 mutation to cause cystinuria in dogs and expand our understanding of this phenotypically and genetically heterogeneous disease, leading to a new classification system for canine cystinuria and better therapeutic management and genetic control in these breeds.