OMIA 002348-9615 : Retinal dysplasia, NDP-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 310600 (trait) , 300658 (gene) , 305390 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: X-linked recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2021

Inheritance: Pedigree analysis in a small family was consistent with an X-linked recessive mode of inheritance (Joyce et al., 2021).

Molecular basis: One affected dog was whole genome sequenced, followed by analysis using a candidate gene approach (COL9A2, COL9A3, NHEJ1, RS1 and NDP genes) and a whole genome approach (WGS was compared with 814 unaffected canids to identify candidate variants). "Candidate variants were tested for appropriate segregation in the ECS family and association with disease was assessed using samples from a total of 180 ECS. ... The same variant in NDP (c.653_654insC, p.Met114Hisfs*16) that was predicted to result in 15 aberrant amino acids before a premature stop in norrin protein, was identified independently by both approaches and was shown to segregate appropriately within the ECS family." (Joyce et al., 2021)

Clinical features: Joyce et al. (2021): "In the original litter examined (seven puppies), two males were found to have behavioural signs suggestive of severe visual deficits (determined by observing their movements in unfamiliar surroundings), absent pupillary light reflexes, wandering nystagmus, darkened irises, and extensive posterior segment haemorrhage. Ocular ultrasonography revealed total retinal detachment and increased echogenicity within posterior segment in all eyes. The globe diameters (anterior to posterior) were comparable with their normal litter mates at 16mm in all dogs except one affected dog, whose globes were 15mm OU. ... One male was found to be bilaterally cryptorchid on clinical examination. ... In the second litter examined (four puppies), one male displayed behavioural signs suggestive of severe visual deficits (determined by observing his movements in unfamiliar surroundings), and was found to have absent dazzle and pupillary light reflexes, a wandering nystagmus, corneal endothelial opacities ventrally in the right eye, darkened irises, hyphema of the right eye and extensive posterior segment haemorrhage in both eyes, with the retina in the left eye appearing detached and as a fibrovascular retrolental mass ..... Ocular ultrasonography revealed total retinal detachment and increased echogenicity within the posterior segment in both eyes. The left globe appeared microphthalmic with an anterior-posterior diameter of 16.42mm versus 21.88mm in the right eye. The affected male was subsequently re-examined, the left eye appeared relatively unchanged whereas the corneal pathology had advanced to diffuse corneal degeneration with neovascularisation and dense crystalline stromal deposits in the right eye .... Microphakia was evident along with incipient nuclear cataract being present ... . On clinical examination the dog was found to be cryptorchid at 10 months old."

Breed: English Cocker Spaniel.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
NDP Norrie disease (pseudoglioma) Canis lupus familiaris X NC_051843.1 (38063932..38037857) NDP 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 Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1315 English Cocker Spaniel Retinal dysplasia NDP insertion, small (<=20) Naturally occurring variant CanFam3.1 X g.37950668_37950668insC c.653_654insC p.(M114Hfs*16) 2021 33945575

Reference


2021 Joyce, H., Burmeister, L.M., Wright, H., Fleming, L., Oliver, J.A.C., Mellersh, C. :
Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog. PLoS One 16:e0251071, 2021. Pubmed reference: 33945575. DOI: 10.1371/journal.pone.0251071.

Edit History


  • Created by Imke Tammen2 on 26 May 2021
  • Changed by Imke Tammen2 on 26 May 2021