An ADAMTS17 splice donor site mutation in dogs with primary lens luxation

Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4716-21. doi: 10.1167/iovs.09-5142. Epub 2010 Apr 7.


Purpose: To identify the genetic cause of isolated canine ectopia lentis, a well-characterized veterinary disease commonly referred to as primary lens luxation (PLL) and to compare the canine disease with a newly described human Weill-Marchesani syndrome (WMS)-like disease of similar genetic etiology.

Methods: Genomewide association analysis and fine mapping by homozygosity were used to identify the chromosomal segment harboring the PLL locus. The resequencing of a regional candidate gene was used to discover a mutation in a splice donor site predicted to cause exon skipping. Exon skipping was confirmed by reverse transcription-polymerase chain reaction amplification of RNA isolated from PLL-affected eyes and from skin fibroblast cultures from PLL-affected dogs. An allelic discrimination assay was used to genotype individual dogs at the splice donor site mutation.

Results: The PLL locus was mapped to a 664-kb region of canine chromosome 3 containing regional candidate gene ADAMTS17. Resequencing ADAMTS17 revealed a GT-->AT splice-donor-site mutation at the 5' end of intron 10. The predicted exon 10 skipping and resultant frame shift were confirmed with RNA derived from PLL-affected dogs. The ADAMTS17 mutation was significantly associated with clinical PLL in three different dog breeds.

Conclusions: A truncating mutation in canine ADAMTS17 causes PLL, a well-characterized veterinary disease, which can now be compared to a recently described rare WMS-like disease caused by truncating mutations of the human ADAMTS17 ortholog.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics*
  • Animals
  • Chromosome Mapping
  • Dog Diseases / genetics*
  • Dogs
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Lens Subluxation / genetics*
  • Lens Subluxation / veterinary*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • RNA Splice Sites / genetics
  • Weill-Marchesani Syndrome / genetics*


  • RNA Splice Sites
  • ADAM Proteins