Primary Lens Luxation (PLL)

 

Gene: ADAMTS17

Transmission: Autosomal recessive (or autosomal dominant with variable expression)

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Common mutation: Substitution (splicing error), ADAMTS17 gene; c.1473+1 G>A, intron10-11

Chinese Shar-Pei mutation: Deletion, ADAMTS17 gene; c.3069_3074 del, p.(V1024_V1025 del), exon22

Medical system: Ocular

Breeds: American Staffordshire Terrier/Amstaff, Australian Cattle Dog, Australian Stumpy Tailed Cattle Dog, Basset Hound, Beagle, Border Collie, Boxer, Bull Terrier, Bull Terrier-Miniature, Catahoula Leopard Dog, Cavalier King Charles Spaniel, Chihuahua, Chinese Crested, Dachshund Miniature Longhair/Shorthair, Fox Terrier, Fox Terrier - Toy, Fox Terrier - Wire, German Shepherd, Great Pyrenees, Jack Russell Terrier, Jagdterrier/German Hunting Terrier, Labrador Retriever, Lancashire Heeler, Maltese Terrier, McNab Shepherd, Miniature American Shepherd, Miniature Pinscher, Parson Russell Terrier, Patterdale Terrier, Pembroke Welsh Corgi, Pomeranian, Portuguese Podengo, Pug, Pumi, Rat Terrier, Russell Terrier, Schnauzer - Miniature, Scottish Terrier, Sealyham Terrier, Shar Pei, Shih Tzu, Tenterfield Terrier, Tibetan Spaniel, Tibetan Terrier, Volpino Italiano, Welsh Terrier, Yorkshire Terrier

Age of onset of symptoms: Between 2 and 8 years

The lens is responsible for the clarity of vision. It is normally held in position within the eye by small fibers called the zonule. When these fibers become brittle and tear, the lens breaks loose and moves freely inside the eye. Then follows a luxation of the lens causing it to either settle in the anterior chamber directly behind the cornea or to slip backwards into the vitreous body. Affected dogs typically show symptoms of irritation, excessive eyelid flutter and excessive tear formation. Lens luxation in one eye is often followed by lens luxation in the other eye within weeks or months.  The visual ability of these dogs cannot remain intact without performing a lens operation as quickly as possible.  It is possible to replace the missing lens with an artificial lens.

 

References:

OMIA link: [0588-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Tzouganakis I, Tsvetanova A, Jeanes EC, et al. (2022) Investigation of the allele frequency of the G>A intron 10 ADAMTS17 mutation causing primary lens luxation in the Portuguese Podengo breed. Vet Ophthalmol 25:85-89.  [pubmed/34870369]

Genetics Committee of the American College of Veterinary Ophthalmologists. (2021) The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition.  [https://ofa.org/wp-content/uploads/2022/10/ACVO-Blue-Book-2021.pdf]

Oliver JAC, Rustidge S, Pettitt L, et al. (2018) Evaluation of ADAMTS17 in Chinese Shar-Pei with primary open-angle glaucoma, primary lens luxation, or both. Am J Vet Res. 79(1):98-106.  [pubmed/29287154]

Graham KL, McCowan C, White A. (2017) Genetic and Biochemical Biomarkers in Canine Glaucoma. Vet Pathol. 54(2):194-203. [pubmed/27681326]

Gharahkhani P, O’Leary CA, Duffy DL, Kyaw-Tanner M. (2015) Potential Modifying Loci Associated With Primary Lens Luxation, Pedal Hyperkeratosis, and Ocular Phenotypes in Miniature Bull Terriers. Invest Ophthalmol Vis Sci 56:8288-96. [pubmed/26720482]

Komáromy AM, Petersen-Jones SM. (2015) Genetics of Canine Primary Glaucomas. Vet Clin North Am Small Anim Pract. 45(6):1159-82. [pubmed/26277300]

Oliver JA, Forman OP, Pettitt L, Mellersh CS. (2015) Two Independent Mutations in ADAMTS17 Are Associated with Primary Open Angle Glaucoma in the Basset Hound and Basset Fauve de Bretagne Breeds of Dog.  PLoS One. 10(10):e0140436. [pubmed/26474315]

Gould D, Pettitt L, McLaughlin B, et al. (2011) ADAMTS17 mutation associated with primary lens luxation is widespread among breeds.  Vet Ophthalmol 14(6):378-384. [pubmed/22050825]

Farias FH, Johnson GS, Taylor JF, et al. (2010) An ADAMTS17 splice donor site mutation in dogs with primary lens luxation.  Investigative Ophthalmology and Visual Science 51(9),4716-4721. [pubmed/20375329]