OMIA 001870-9615 : Glaucoma, primary open angle, ADAMTS10-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 137760

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: Primary open angle glaucoma

Species-specific symbol: POAG

Inheritance: From a colony of Beagles with POAG, established in 1972 (Gelatt, 1972; Gelatt et al., 1977), Gelatt and Gum (1981) provided substantial evidence of autosomal recessive inheritance.

Mapping: By genotyping "19 affected and 10 carrier dogs from the POAG Beagle colony using version 2 of the Affymetrix Canine Genome SNP array", Kuchtey et al. (2011) conducted a GWAS that mapped the POAG locus to a 4Mb region on chromosome CFA20.

Molecular basis: By sequencing one affected, one carrier and one normal dog from the POAG Beagle colony, for the entire 4MB candidate region described in the Mapping section above, Kuchtey et al. (2011) identified the causal mutation as a "56097365 G->A variant [Gly661Arg] . . . within exon 17 of ADAMTS10, a member of the disintegrin and metalloproteinase with thrombospondin motifs family of secreted proteases involved in formation of the extracellular matrix". The authors noted that "glycine at position 661 is completely conserved in 38 vertebrate species". By genotyping Beagle dogs not belonging to the POAG Beagle colony, Kuchtey et al. (2013) provided strong supportive evidence for the 56097365 G->A variant [Gly661Arg] being a causal mutant of POAG in this breed.

Kanemaki et al. (2013) provided evidence that variants in ADAMTS10 are not causal for this disorder in Shiba-Inus and Shih-Tzus, but that variants in SRBD1 (another comparative candidate gene) "play an important role in glaucoma pathology in both Shiba-Inus and Shih-Tzus".

Ahonen et al. (2014) reported a different likely causal mutation in Norwegian Elkhound: "A fully segregating missense mutation (p.A387T) in exon 9 was found in 14 cases and 572 unaffected NEs (pFisher = 3.5×10-27) with a high carrier frequency (25.3%). The mutation interrupts a highly conserved residue in the metalloprotease domain of ADAMTS10, likely affecting its functional capacity".

Breeds: Beagle, Norwegian Elkhound, Shiba-Inu, Shih-Tzu.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ADAMTS10 ADAM metallopeptidase with thrombospondin type 1 motif, 10 Canis lupus familiaris 20 NC_006602.3 (53110533..53090819) ADAMTS10 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.

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
Beagle Glaucoma, primary open angle ADAMTS10 missense p.G661R 2011 21379321
Norwegian Elkhound Glaucoma, primary open angle ADAMTS10 missense CanFam3.1 20 g.53101896G>A c.1159G>A p.A387T 2014 25372548 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.
2017 Graham, K.L., McCowan, C., White, A. :
Genetic and Biochemical Biomarkers in Canine Glaucoma. Vet Pathol 54:194-203, 2017. Pubmed reference: 27681326. DOI: 10.1177/0300985816666611.
2016 Boote, C., Palko, J.R., Sorensen, T., Mohammadvali, A., Elsheikh, A., Komáromy, A.M., Pan, X., Liu, J. :
Changes in posterior scleral collagen microstructure in canine eyes with an ADAMTS10 mutation. Mol Vis 22:503-17, 2016. Pubmed reference: 27212875.
Palko, J.R., Morris, H.J., Pan, X., Harman, C.D., Koehl, K.L., Gelatt, K.N., Plummer, C.E., Komáromy, A.M., Liu, J. :
Influence of Age on Ocular Biomechanical Properties in a Canine Glaucoma Model with ADAMTS10 Mutation. PLoS One 11:e0156466, 2016. Pubmed reference: 27271467. DOI: 10.1371/journal.pone.0156466.
2015 Komáromy, A.M., Petersen-Jones, S.M. :
Genetics of Canine Primary Glaucomas. Vet Clin North Am Small Anim Pract 45:1159-82, v, 2015. Pubmed reference: 26277300. DOI: 10.1016/j.cvsm.2015.06.003.
Pizzirani, S. :
Definition, Classification, and Pathophysiology of Canine Glaucoma. Vet Clin North Am Small Anim Pract 45:1127-57, v, 2015. Pubmed reference: 26456751. DOI: 10.1016/j.cvsm.2015.06.002.
2014 Ahonen, S.J., Kaukonen, M., Nussdorfer, F.D., Harman, C.D., Komáromy, A.M., Lohi, H. :
A novel missense mutation in ADAMTS10 in Norwegian Elkhound primary glaucoma. PLoS One 9:e111941, 2014. Pubmed reference: 25372548. DOI: 10.1371/journal.pone.0111941.
2013 Kuchtey, J., Kunkel, J., Esson, D., Sapienza, J.S., Ward, D.A., Plummer, C.E., Gelatt, K.N., Kuchtey, R.W. :
Screening ADAMTS10 in dog populations supports Gly661Arg as the glaucoma-causing variant in Beagles. Invest Ophthalmol Vis Sci 54:1881-6, 2013. Pubmed reference: 23422823. DOI: 10.1167/iovs.12-10796.
Palko, J.R., Iwabe, S., Pan, X., Agarwal, G., Komáromy, A.M., Liu, J. :
Biomechanical Properties and Correlation With Collagen Solubility Profile in the Posterior Sclera of Canine Eyes With an ADAMTS10 Mutation. Invest Ophthalmol Vis Sci 54:2685-95, 2013. Pubmed reference: 23518772. DOI: 10.1167/iovs.12-10621.
2012 Kato, K., Sasaki, N., Shastry, B.S. :
Retinal ganglion cell (RGC) death in glaucomatous Beagles is not associated with mutations in p53 and NTF4 genes. Vet Ophthalmol 15 Suppl 2:8-12, 2012. Pubmed reference: 22524196. DOI: 10.1111/j.1463-5224.2012.01024.x.
2011 Kuchtey, J., Olson, L.M., Rinkoski, T., Mackay, E.O., Iverson, T.M., Gelatt, K.N., Haines, J.L., Kuchtey, R.W. :
Mapping of the disease locus and identification of ADAMTS10 as a candidate gene in a canine model of primary open angle glaucoma. PLoS Genet 7:e1001306, 2011. Pubmed reference: 21379321. DOI: 10.1371/journal.pgen.1001306.
2009 Kato, K., Kamida, A., Sasaki, N., Shastry, BS. :
Evaluation of the CYP1B1 gene as a candidate gene in Beagles with primary open-angle glaucoma (POAG). Mol Vis 15:2470-4, 2009. Pubmed reference: 1428571.
2008 Mackay, E.O., Källberg, M.E., Gelatt, K.N. :
Aqueous humor myocilin protein levels in normal, genetic carriers, and glaucoma Beagles. Vet Ophthalmol 11:177-85, 2008. Pubmed reference: 18435660. DOI: 10.1111/j.1463-5224.2008.00617.x.
1995 Brooks, D.E., Strubbe, D.T., Kubilis, P.S., Mackay, E.O., Samuelson, D.A., Gelatt, K.N. :
Histomorphometry of the optic nerves of normal dogs and dogs with hereditary glaucoma Experimental Eye Research 60:71-89, 1995. Pubmed reference: 7720807.
1981 Gelatt, K.N., Gum, G.G. :
Inheritance of primary glaucoma in the Beagle. Am J Vet Res 42:1691-3, 1981. Pubmed reference: 7325430.
1980 Peiffer, R.L., Gum, G.G., Grimson, R.C., Gelatt, K.N. :
Aqueous humor outflow in Beagles with inherited glaucoma: constant pressure perfusion. Am J Vet Res 41:1808-13, 1980. Pubmed reference: 7212410.
1977 Gelatt, K.N., Peiffer, R.L., Gwin, R.M., Gum, G.G., Williams, L.W. :
Clinical manifestations of inherited glaucoma in the beagle. Invest Ophthalmol Vis Sci 16:1135-42, 1977. Pubmed reference: 924743.
1972 Gelatt, K.N. :
Familial glaucoma in the Beagle dog Journal of the American Animal Hospital Association 8:23-28, 1972.

Edit History


  • Created by Frank Nicholas on 22 Aug 2013
  • Changed by Frank Nicholas on 22 Aug 2013
  • Changed by Frank Nicholas on 20 Sep 2013
  • Changed by Frank Nicholas on 25 May 2016