OMIA 001976-9615 : Glaucoma, primary open angle, ADAMTS17-related in Canis lupus familiaris

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: 2015

Species-specific symbol: POAG

Markers: Jeanes et al. (2019) showed that the likely causal variants for this disorder are significantly associated with height in the Petit Basset Griffon Vendeen and Shar Pei breeds, "with affected individuals being significantly shorter on average than both carriers of the mutation and clear dogs", suggesting "that selecting dogs to be of a specific short height may have increased the frequency of the mutations within these breeds".

Molecular basis: In Basset Hounds, Oliver et al. (2015) reported a likely causal mutation: "a 19 bp deletion in exon 2 that alters the reading frame and is predicted to lead to a truncated protein" (CanFam3.1 chr3:40,614,853–40,614,872).

In Basset Fauve de Bretagne dogs, the same authors reported a likely causal mutation in the same gene: "a missense mutation in exon 11 causing a glycine to serine amino acid substitution ([CanFam3.1 chr3:40,808,345; c.1552G>A]; G519S) in the disintegrin-like domain of ADAMTS17 which is predicted to alter protein function".

Forman et al. (2015) reported a different likely causal variant in the Petit Basset Griffon Vendéen breed, namely "a 4.96 Mb inversion . . . with breakpoints in intron 12 of ADAMTS17 (chr3:40,812,274) and a downstream intergenic region (chr3:45,768,123)".

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."

Breeds: Basset Fauve de Bretagne, Basset Hound, 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. 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
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
Petit Basset Griffon Vendéen Glaucoma, primary open angle, ADAMTS17-related ADAMTS17 inversion CanFam3.1 Forman et al. (2015): "a 4.96 Mb inversion . . . with breakpoints in intron 12 of ADAMTS17 (chr3:40,812,274) and a downstream intergenic region (chr3:45,768,123)". 2015 26683476
Basset Hound Glaucoma, primary open angle, ADAMTS17-related ADAMTS17 deletion, small (<=20) CanFam3.1 3 g.40614853_40614872del "19 bp deletion in exon 2 of ADAMTS17 (CanFam3.1 chr3:40,614,853-40,614,872)" 2015 26474315
Basset Fauve de Bretagne Glaucoma, primary open angle, ADAMTS17-related ADAMTS17 missense CanFam3.1 3 g.40808345G>A c.1552G>A p.G518S 2015 26474315 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.
2019 Jeanes, E.C., Oliver, J.A.C., Ricketts, S.L., Gould, D.J., Mellersh, C.S. :
Glaucoma-causing <i>ADAMTS17</i> mutations are also reproducibly associated with height in two domestic dog breeds: selection for short stature may have contributed to increased prevalence of glaucoma. Canine Genet Epidemiol 6:5, 2019. Pubmed reference: 31131111. DOI: 10.1186/s40575-019-0071-6.
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 Bedford, P.G. :
Open-angle glaucoma in the Petit Basset Griffon Vendeen. Vet Ophthalmol 20:98-102, 2017. Pubmed reference: 26945802. DOI: 10.1111/vop.12369.
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 Oliver, J.A., Forman, O.P., Pettitt, L., Mellersh, C.S. :
Correction: 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 11:e0156192, 2016. Pubmed reference: 27192202. DOI: 10.1371/journal.pone.0156192.
2015 Forman, O.P., Pettitt, L., Komáromy, A.M., Bedford, P., Mellersh, C. :
A Novel Genome-Wide Association Study Approach Using Genotyping by Exome Sequencing Leads to the Identification of a Primary Open Angle Glaucoma Associated Inversion Disrupting ADAMTS17. PLoS One 10:e0143546, 2015. Pubmed reference: 26683476. DOI: 10.1371/journal.pone.0143546.
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.
Oliver, J.A., Forman, O.P., Pettitt, L., Mellersh, C.S. :
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:e0140436, 2015. Pubmed reference: 26474315. DOI: 10.1371/journal.pone.0140436.
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.

Edit History


  • Created by Frank Nicholas on 30 Dec 2015
  • Changed by Frank Nicholas on 30 Dec 2015
  • Changed by Frank Nicholas on 19 Jan 2018
  • Changed by Frank Nicholas on 30 May 2019