Open AccessSLC 3A1 and SLC 7A9 Mutations in Autosomal Recessive or Dominant Canine Cystinuria: A New Classification System
Author(s) -
Brons A.K.,
Henthorn P.S.,
Raj K.,
Fitzgerald C.A.,
Liu J.,
Sewell A.C.,
Giger U.
Publication year - 2013
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/jvim.12176
Subject(s) - cystinuria , genetics , frameshift mutation , breed , biology , mutation , missense mutation , cystine , exon , medicine , stop codon , gene , biochemistry , cysteine , enzyme
Background Cystinuria, one of the first recognized inborn errors of metabolism, has been reported in many dog breeds. Hypothesis/Objectives To determine urinary cystine concentrations, inheritance, and mutations in the SLC 3A1 and SLC 7A9 genes associated with cystinuria in 3 breeds. Animals 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. Methods Urinary cystinuria and aminoaciduria was assessed and exons of the SLC 3A1 and SLC 7A9 genes were sequenced from genomic DNA . Results In each breed, male and female dogs, independent of neuter status, were found to form calculi. A frameshift mutation in SLC 3A1 (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 SLC 3A1 was found in autosomal‐dominant ( AD ) cystinuria with a more severe phenotype in homozygous than in heterozygous Australian Cattle Dogs. A missense mutation in SLC 7A9 (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 SLC 7A9 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.