Categories: Vision / eye phene

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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: