OMIA 000588-9615 : Lens luxation in Canis lupus familiaris

In other species: domestic cat

Possibly relevant human trait(s) and/or gene(s) (MIM number): 613195

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2010

Species-specific name: Primary lens luxation; isolated canine ectopia lentis

Species-specific symbol: PPL

Mapping: Sargan et al. (2007) conducted a genome scan with 364 microsatellites on "23 PLL-affected miniature bull terriers, together with an equal number of obligate PLL carriers with no luxation, and also 23 PLL-affected Lancashire heeler, with an equal number of obligate carriers with no luxation". A linkage analysis highlighted "a 6.3-Mbp region in the central part of chromosome 3".

By conducting a GWAS on 28 affected and 20 control Jack Russell Terriers, each genotyped with the CanineSNP20 BeadChip, Farias et al. (2010) highlighted the same region on chromosome CFA3 as identified by Sargan et al. (2008). Subsequent fine-mapping narrowed the region to a 664kb segment harbouring the positional candidate gene ADAMTS17.

Molecular basis: By sequencing the positional candidate gene ADAMTS17, Farias et al. (2010) identified the causal mutation as "a G→A transition at c.1473+1, which destroys the splice donor recognition site in intron 10".

Oliver et al. (2018): "All affected [Primary open-angle glaucoma (POAG), primary lens luxation (PLL), or both] Shar-Pei were homozygous for a 6-bp deletion in exon 22 of ADAMTS17 predicted to affect the resultant protein. All unaffected Shar-Pei were heterozygous or homozygous for the wild-type allele. The variant sequence was significantly associated with affected status (diagnosis of POAG, PLL, or both). All dogs of other breeds were homozygous for the wild-type allele. The cDNA sequencing confirmed presence of the expected variant mRNA sequence in ocular tissue from the affected dog only. Gene expression analysis revealed a 4.24-fold decrease in the expression of ADAMTS17 in ocular tissue from the affected dog."

Breed: Chinese Shar-Pei.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ADAMTS17 ADAM metallopeptidase with thrombospondin type 1 motif, 17 Canis lupus familiaris 3 NC_006585.3 (40613902..40939616) ADAMTS17 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Chinese Shar-Pei Primary open-angle glaucoma (POAG), primary lens luxation (PLL), or both ADAMTS17 deletion, small (<=20) CanFam 3.1 3 g.40935387_40935392delCGTGGT c.3070_3075delCGTGGT p.Val1025_Val1026del 2018 29287154
American hairless Chinese Crested Dog Jack Russell Terrier Lens luxation ADAMTS17 splicing CanFam3.1 3 g.40782144G>A c.1473+1G>A 2010 20375329 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2018 Oliver, J.A.C., Rustidge, S., Pettitt, L., Jenkins, C.A., Farias, F.H.G., Giuliano, E.A., Mellersh, C.S. :
Evaluation of ADAMTS17 in Chinese Shar-Pei with primary open-angle glaucoma, primary lens luxation, or both. Am J Vet Res 79:98-106, 2018. Pubmed reference: 29287154. DOI: 10.2460/ajvr.79.1.98.
2015 Gharahkhani, P., O'Leary, C.A., Duffy, D.L., Kyaw-Tanner, M. :
Potential Modifying Loci Associated With Primary Lens Luxation, Pedal Hyperkeratosis, and Ocular Phenotypes in Miniature Bull Terriers. Invest Ophthalmol Vis Sci 56:8288-96, 2015. Pubmed reference: 26720482. DOI: 10.1167/iovs.15-18074.
2014 [No authors listed] :
[Lens luxation in dogs: a retrospective study of 134 dogs (2000-2011)]. Schweiz Arch Tierheilkd 156:125-31, 2014. Pubmed reference: 24568806. DOI: 10.1024/0036-7281/a000562.
Montgomery, K.W., Labelle, A.L., Gemensky-Metzler, A.J. :
Trans-corneal reduction of anterior lens luxation in dogs with lens instability: a retrospective study of 19 dogs (2010-2013). Vet Ophthalmol :, 2014. Pubmed reference: 24405506. DOI: 10.1111/vop.12142.
2013 Bellumori, T.P., Famula, T.R., Bannasch, D.L., Belanger, J.M., Oberbauer, A.M. :
Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010). J Am Vet Med Assoc 242:1549-55, 2013. Pubmed reference: 23683021. DOI: 10.2460/javma.242.11.1549.
2012 Gharahkhani, P., O’Leary, C., Duffy, D., Bernays, M., Kyaw-Tanner, M. :
Primary Lens Luxation in Australian Tenterfield and Miniature Bull Terriers is due to an old ADAMTS17 Mutation and is an Additive Trait. Open Genomics Journal 5:7-13, 2012. DOI: 10.2174/1875693X01205010007.
2011 Gould, D., Pettitt, L., McLaughlin, B., Holmes, N., Forman, O., Thomas, A., Ahonen, S., Lohi, H., O'Leary, C., Sargan, D., Mellersh, C. :
ADAMTS17 mutation associated with primary lens luxation is widespread among breeds. Vet Ophthalmol 14:378-384, 2011. Pubmed reference: 22050825. DOI: 10.1111/j.1463-5224.2011.00892.x.
2010 Farias, FH., Johnson, GS., Taylor, JF., Giuliano, E., Katz, ML., Sanders, DN., Schnabel, RD., McKay, SD., Khan, S., Gharahkhani, P., O'Leary, CA., Pettitt, L., Forman, OP., Boursnell, M., Mclaughlin, B., Ahonen, S., Lohi, H., Hernandez-Merino, E., Gould, DJ., Sargan, D., Mellersh, CS. :
An ADAMTS17 Splice Donor Site Mutation in Dogs with Primary Lens Luxation. Invest Ophthalmol Vis Sci :, 2010. Pubmed reference: 20375329. DOI: 10.1167/iovs.09-5142.
2009 Stuhr, CM., Schilke, HK., Forte, C. :
Intracapsular lensectomy and sulcus intraocular lens fixation in dogs with primary lens luxation or subluxation. Vet Ophthalmol 12:357-60, 2009. Pubmed reference: 19883465. DOI: 10.1111/j.1463-5224.2009.00731.x.
2008 Oberbauer, AM., Hollingsworth, SR., Belanger, JM., Regan, KR., Famula, TR. :
Inheritance of cataracts and primary lens luxation in Jack Russell Terriers. Am J Vet Res 69:222-7, 2008. Pubmed reference: 18241019. DOI: 10.2460/ajvr.69.2.222.
2007 Sargan, DR., Withers, D., Pettitt, L., Squire, M., Gould, DJ., Mellersh, CS. :
Mapping the mutation causing lens luxation in several terrier breeds. J Hered 98:534-8, 2007. Pubmed reference: 17573382. DOI: 10.1093/jhered/esm029.
2004 Ketteritzsch, K., Hamann, H., Brahm, R., Grussendorf, H., Rosenhagen, C.U., Distl, O. :
Genetic analysis of presumed inherited eye diseases in Tibetan Terriers. Vet J 168:151-9, 2004. Pubmed reference: 15301763. DOI: 10.1016/j.tvjl.2003.08.005.
Ketteritzsch, K., Hamann, H., Brahm, R., Grussendorf, H., Rosenhagen, CU., Distl, O. :
Genetic analysis of presumed inherited eye diseases in Tibetan Terriers. Vet J 168:151-9, 2004. Pubmed reference: 15301758. DOI: 10.1016/S1090-0233(03)00143-6.
1998 Lazarus, JA., Pickett, JP., Champagne, ES. :
Primary lens luxation in the Chinese Shar Pei: clinical and hereditary characteristics. Vet Ophthalmol 1:101-107, 1998. Pubmed reference: 11397217.
1990 Curtis, R. :
Lens Luxation in the Dog and Cat Veterinary Clinics of North America-Small Animal Practice 20:755-773, 1990. Pubmed reference: 2194357.
1983 Curtis, R. :
Aetiopathological aspects of inherited lens dislocation in the Tibetan Terrier. J Comp Pathol 93:151-63, 1983. Pubmed reference: 6601667.
Curtis, R., Barnett, KC., Lewis, SJ. :
Clinical and pathological observations concerning the aetiology of primary lens luxation in the dog. Vet Rec 112:238-46, 1983. Pubmed reference: 6601878.
Curtis, R., Barnett, KC., Startup, FG. :
Primary lens luxation in the miniature bull terrier. Vet Rec 112:328-30, 1983. Pubmed reference: 6602414.
1982 Curtis, R. :
Hereditary luxation of the canine lens. Animal health trust small animals centre, newmarket. Trans Ophthalmol Soc U K 102 Pt 3:398-402, 1982. Pubmed reference: 6985238.
1980 Curtis, R., Barnett, KC. :
Primary lens luxation in the dog. J Small Anim Pract 21:657-68, 1980. Pubmed reference: 6969820.
1979 Willis, M.B., Barnett, K.C., Tempest, W.M. :
Genetic aspects of lens luxation in the Tibetan Terrier Veterinary Record 104:409-412, 1979. Pubmed reference: 314700.
1978 Barnett, K.C., Curtis, R. :
Lens luxation and progressive retinal atrophy in the Tibetan Terrier Veterinary Record :160 only, 1978. Pubmed reference: 308725.
1971 Gelatt, K.N. :
Glaucoma and lens luxation in a dog Veterinary Medicine and Small Animal Clinician 66:1102-1104, 1971. Pubmed reference: 5209417.
1970 Chandler, E.A. :
Lens luxation in the Webster Terrier Veterinary Record 86:145-146, 1970. Pubmed reference: 5461252.
1969 Lawson, DD. :
Luxation of the crystalline lens in the dog. J Small Anim Pract 10:461-3, 1969. Pubmed reference: 5387868.

Edit History


  • Created by Frank Nicholas on 09 Aug 2010
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 21 May 2013
  • Changed by Frank Nicholas on 19 Jan 2018