A Carbohydrate Sulfotransferase-6 (CHST6) gene mutation is associated with Macular Corneal Dystrophy in Labrador Retrievers.

PURPOSE To locate and identify variants associated with macular corneal dystrophy (MCD) in Labrador Retriever (LR) dogs, in the candidate gene carbohydrate sulfotransferase-6 (CHST6). METHODS The single coding exon of canine CHST6 was sequenced in one affected LR with MCD and one control LR clinically clear of ocular disease. A further 71 control LR with unknown clinical status were sequenced for the putative causal variant in CHST6. A TaqMan SNP genotyping assay was developed and used to screen an additional 84 dogs (five affected LR and 79 clinically clear LR). Finally, the variant was screened in a third cohort of 89 unrelated LR with unknown clinical status to estimate its allele frequency in the population of LR in the United Kingdom. RESULTS A single nucleotide polymorphism (SNP) was identified within the coding exon of CHST6, resulting in a missense mutation (c.814C>A, p.R272S). All six LR affected with MCD were homozygous for the mutant allele, while 140/151 control LR were homozygous for the wild-type allele and 11/151 were heterozygous for the mutation, indicating an association with MCD (P < 10-5 ). The mutant allele was present in the unrelated LR cohort at a frequency of 0.017, suggesting carrier and affection rates of 3.3% and 0.028%, respectively. CONCLUSIONS A missense mutation in the CHST6 gene is strongly associated with autosomal recessive MCD in the LR.