OMIA:001871-9615 : Glaucoma, primary closed-angle in Canis lupus familiaris (dog)

Categories: Vision / eye phene

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: no

Species-specific description: This disorder in Dandie Dinmont Terriers was first described by Ahonen et al. (2013). Several studies investigated the condition in Basset Hounds (Ahram et al.,2014, 2015; Oliver et al., 2019). Park et al. (2022) reported that "the American Cocker Spaniel (ACS) is among the most common breeds observed with PACG [primary angle closure glaucoma] development in dogs."

Mapping: Ahonen et al. (2013) conducted a GWAS on 23 affected and 23 control Dandie Dinmot Terriers, each genotyped with the Illumina’s Canine SNP20 BeadChip, yielding 13, 560 informative SNPs. Analysis "revealed a 9.5 Mb associated region with genome wide significance ranging from 20040105 bp to 29518099 bp on CFA8 (build 2.1 of the canine genome reference sequence)". Subsequent fine mapping narrowed the candidate region to 1.6Mb, containing seven protein-coding genes. Mutation screening in the most likely five of these failed to reveal a causal mutation. From a GWAS in Basset Hounds, Ahram et al. (2014) identified two regions on chromosomes CFA14 and CFA24. In a different Basset Hound cohort, Ahram et al. (2015) identified a 1.82Mbp region on chromosome CFA19q. A GWAS on European Basset Hounds highlighted "1.4 and 0.2 Mb regions, on chromosomes 24 and 37, respectively" (Oliver et al., 2019) Park et al. (2022) "sought to identify genetic risk factors to explain the high prevalence of PACG in ACSs [American Cocker Spaniels] by using a case-control breed-matched genome-wide association study. However, the GWAS failed to identify candidate loci associated with PACG in this breed. This study then assessed intrinsic ocular morphologic traits that may relate to PACG susceptibility in this breed."

Molecular basis: Ahram et al. (2015) reported a potentially pathogenic missense mutation in the nebulin gene (NEB) (g.5588214 A->G in exon 48; p.2051 Lys->Arg), which is located in their candidate region of CFA19q, as being strongly (but not completely) associated with the disorder in Basset Hounds.

Breeds: American Cocker Spaniel (Dog) (VBO_0200038), Basset Hound (Dog) (VBO_0200126), Dandie Dinmont Terrier (Dog) (VBO_0200429).
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
NEB nebulin Canis lupus familiaris - no genomic information (-..-) NEB Homologene, Ensembl , NCBI gene

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001871-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2022 Park, S., Casanova, M.I., Bannasch, D.L., Daley, N.L., Kim, S., Kuchtey, J., Gomes, F.E., Leonard, B.C., Good, K.L., Martins, B.D.C., Murphy, C.J., Thomasy, S.M. :
Ocular morphologic traits in the American Cocker Spaniel may confer primary angle closure glaucoma susceptibility. Sci Rep 12:18980, 2022. Pubmed reference: 36348026. DOI: 10.1038/s41598-022-23238-1.
2021 Genetics Committee of the American College of Veterinary Opthalmologists :
The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition , 2021.
Pumphrey, S.A., Zitek-Morrison, E., Pizzirani, S., Meola, D.M. :
Evaluation of matrix metalloproteinases and tissue inhibitors of metalloproteinases in aqueous humor of dogs with versus without naturally occurring primary angle-closure glaucoma. Am J Vet Res :1-11, 2021. Pubmed reference: 34936570. DOI: 10.2460/ajvr.21.04.0062.
Yun, S., Lee, D., Kang, S., Kim, D.W., Kim, Y., Cho, J.Y., Seo, K. :
Proteomic analysis of aqueous humor in canine primary angle-closure glaucoma in American Cocker Spaniel dogs. Vet Ophthalmol 24:520-532, 2021. Pubmed reference: 34558166. DOI: 10.1111/vop.12937.
2019 Oliver, J.A.C., Ricketts, S.L., Kuehn, M.H., Mellersh, C.S. :
Primary closed angle glaucoma in the Basset Hound: Genetic investigations using genome-wide association and RNA sequencing strategies. Mol Vis 25:93-105, 2019. Pubmed reference: 30820145.
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.
2015 Ahram, D.F., Grozdanic, S.D., Kecova, H., Henkes, A., Collin, R.W., Kuehn, M.H. :
Variants in nebulin (NEB) are linked to the development of familial primary angle closure glaucoma in Basset Hounds. PLoS One 10:e0126660, 2015. Pubmed reference: 25938837. DOI: 10.1371/journal.pone.0126660.
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.
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.
Pearl, R., Gould, D., Spiess, B., Pearl, R., Gould, D., Spiess, B. :
Progression of pectinate ligament dysplasia over time in two populations of Flat-Coated Retrievers. Vet Ophthalmol 18:6-12, 2015. Pubmed reference: 24025050. DOI: 10.1111/vop.12098.
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 Ahram, D.F., Cook, A.C., Kecova, H., Grozdanic, S.D., Kuehn, M.H. :
Identification of genetic loci associated with primary angle-closure glaucoma in the basset hound. Mol Vis 20:497-510, 2014. Pubmed reference: 24791135.
2013 Ahonen, S.J., Pietilä, E., Mellersh, C.S., Tiira, K., Hansen, L., Johnson, G.S., Lohi, H. :
Genome-wide association study identifies a novel canine glaucoma locus. PLoS One 8:e70903, 2013. Pubmed reference: 23951034. DOI: 10.1371/journal.pone.0070903.

Edit History

  • Created by Frank Nicholas on 22 Aug 2013
  • Changed by Frank Nicholas on 22 Aug 2013
  • Changed by Frank Nicholas on 17 May 2015
  • Changed by Frank Nicholas on 24 Jan 2018
  • Changed by Frank Nicholas on 21 Sep 2019
  • Changed by Imke Tammen2 on 03 Oct 2021
  • Changed by Imke Tammen2 on 14 Jan 2022
  • Changed by Imke Tammen2 on 15 Nov 2022
  • Changed by Imke Tammen2 on 07 May 2023
  • Changed by Imke Tammen2 on 17 Jun 2023