OMIA:000588-9615 : Lens luxation in Canis lupus familiaris (dog)

In other species: domestic cat

Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 613195 (trait) , 607511 (gene)

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; luxatio lentis

Species-specific symbol: PPL

Species-specific description: see also OMIA 001976-9615 : Glaucoma, primary open angle, ADAMTS17-related in Canis lupus familiaris

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". Gould et al. (2011) "screened 121 dogs of 30 different breeds that were clinically affected with PLL for the previously described ADAMTS17 mutation [OMIA variant:365]. ... In addition to the three previously reported breeds we identified at least one dog of each of 14 different breeds that was homozygous for the ADAMTS17 mutation and clinically affected (Australian Cattle dog, Chinese crested dog, Jagdterrier [also known as the German hunt terrier], Parson Russell terrier, Patterdale terrier, Rat terrier, Sealyham terrier, Tenterfield terrier, Tibetan terrier, Toy fox terrier, Volpino Italiano, Welsh terrier, Wire-haired fox terrier, Yorkshire terrier). 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."

Clinical features: The clinical features associated with primary lens luxation (PLL) are changes to eye lens stability in both eyes, with varying severity of clinical signs associated with each eye. PLL typically goes undetected until the lens displaces in one eye. Dogs typically present with concurrent partial lens displacement of the other eye, which progresses into full displacement weeks to months later (Farias et al., 2010; Colitz & O’Connell, 2015). The lens usually moves anteriorly causing disruption to the pupil and draining mechanism in the eye, leading to acute glaucoma (Gould et al., 2011; Gharahkhani et al., 2015). IT thanks DVM student Zoe Levesque, who provided the basis of this contribution in May 2023.

Prevalence: Tzouganakis et al. (2022) genotyped 82 Portuguese Podengo dogs in the UK genotyping for the ADAMTS17:c.1473+1G>A mutation. The allele frequency for the variant was estimated calculated as 0.09.

Breeds: American Toy Terrier (Dog) (VBO_0200057), Australian Cattle Dog (Dog) (VBO_0200088), Border Collie (Dog) (VBO_0200193), Chinese Crested (Dog) (VBO_0200345), Chinese Shar-Pei (Dog) (VBO_0200351), German Hunting Terrier (Dog) (VBO_0200568), Jack Russell Terrier (Dog) (VBO_0200724), Lancashire Heeler (Dog) (VBO_0200808), Miniature Bull Terrier (Dog) (VBO_0200882), Parson Russell Terrier (Dog) (VBO_0200987), Patterdale Terrier (Dog) (VBO_0200990), Portuguese Podengo (Dog) (VBO_0201067), Rat Terrier (Dog) (VBO_0201125), Sealyham Terrier (Dog) (VBO_0201200), Tenterfield Terrier (Dog) (VBO_0201342), Tibetan Terrier (Dog) (VBO_0201353), Toy Fox Terrier (Dog) (VBO_0201361), Volpino Italiano (Dog) (VBO_0201390), Welsh Terrier (Dog) (VBO_0201412), Wire Fox Terrier (Dog) (VBO_0201424), Yorkshire Terrier (Dog) (VBO_0201448).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

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_051807.1 (41014731..41340884) ADAMTS17 Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
365 American Toy Terrier (Dog) Chinese Crested (Dog) German Hunting Terrier (Dog) Jack Russell Terrier (Dog) Lancashire Heeler (Dog) Miniature Bull Terrier (Dog) Parson Russell Terrier (Dog) Patterdale Terrier (Dog) Rat Terrier (Dog) Sealyham Terrier (Dog) Tenterfield Terrier (Dog) Tibetan Terrier (Dog) Toy Fox Terrier (Dog) Volpino Italiano (Dog) Welsh Terrier (Dog) Wire Fox Terrier (Dog) Yorkshire Terrier (Dog) Lens luxation ADAMTS17 splicing Naturally occurring variant CanFam3.1 3 g.40782144G>A c.1473+1G>A XM_022416850.1; additional breeds reported by PMID:22050825 and PMID:37582787 rs1152388408 2010 20375329 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
942 Chinese Shar-Pei (Dog) Primary open-angle glaucoma (POAG), primary lens luxation (PLL), or both ADAMTS17 deletion, small (<=20) Naturally occurring variant CanFam3.1 3 g.40935387_40935392del c.3069_3074del p.(V1024_V1025del) XM_014112382.2; XP_013967857.1; published as c.3070_3075delCGTGGT; p.(V1025_V1026del) 2018 29287154

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000588-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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.

2023 Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. :
Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787. DOI: 10.1186/s13059-023-03023-7.
2022 Tzouganakis, I., Tsvetanova, A., Jeanes, E.C., Mellersh, C.S., Gould, D.J. :
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, 2022. Pubmed reference: 34870369. DOI: 10.1111/vop.12960.
2021 Genetics Committee of the American College of Veterinary Opthalmologists :
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 , 2021.
2019 Lewis, T.W., Mellersh, C.S. :
Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test. PLoS One 14:e0209864, 2019. Pubmed reference: 30650096. DOI: 10.1371/journal.pone.0209864.
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.
2017 Hubmacher, D., Schneider, M., Berardinelli, S.J., Takeuchi, H., Willard, B., Reinhardt, D.P., Haltiwanger, R.S., Apte, S.S. :
Unusual life cycle and impact on microfibril assembly of ADAMTS17, a secreted metalloprotease mutated in genetic eye disease. Sci Rep 7:41871, 2017. Pubmed reference: 28176809. DOI: 10.1038/srep41871.
2015 Colitz, C.M., O'Connell, K. :
Lens-related emergencies: Not always so clear. Top Companion Anim Med 30:81-5, 2015. Pubmed reference: 26494499. DOI: 10.1053/j.tcam.2015.08.001.
Genetics Committee of the American College of Veterinary Ophthalmologists :
Ocular Disorders Presumed to be Inherited in Purebred Dogs (“The Blue Book”), 8th edition :354-356, 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, F.H., Johnson, G.S., Taylor, J.F., Giuliano, E., Katz, M.L., Sanders, D.N., Schnabel, R.D., McKay, S.D., Khan, S., Gharahkhani, P., O'Leary, C.A., Pettitt, L., Forman, O.P., Boursnell, M., McLaughlin, B., Ahonen, S., Lohi, H., Hernandez-Merino, E., Gould, D.J., Sargan, D.R., Mellersh, C. :
An ADAMTS17 splice donor site mutation in dogs with primary lens luxation. Invest Ophthalmol Vis Sci 51:4716-21, 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.
Saroglu, M., Erdikmen, D.O., Guzel, O., Aydin, D. :
Luxatio lentis in dogs: a case report. Vet Med-Czech. 52:213-222, 2007. DOI: 10.17221/2006-VETMED..
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.
1986 Foster, S.J., Curtis, R., Barnett, K.C. :
Primary lens luxation in the Border Collie. J Small Anim Pract 27:1-6, 1986.
1983 Curtis, R., Barnett, KC., Startup, FG. :
Primary lens luxation in the miniature bull terrier. Vet Rec 112:328-30, 1983. Pubmed reference: 6602414.
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. :
Aetiopathological aspects of inherited lens dislocation in the Tibetan Terrier. J Comp Pathol 93:151-63, 1983. Pubmed reference: 6601667.
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
  • Changed by Frank Nicholas on 01 Nov 2020
  • Changed by Imke Tammen2 on 16 Dec 2021
  • Changed by Imke Tammen2 on 29 Jan 2022
  • Changed by Imke Tammen2 on 07 May 2023
  • Changed by Imke Tammen2 on 04 Jun 2023
  • Changed by Imke Tammen2 on 18 Aug 2023