OMIA 001554-9615 : Multifocal retinopathy 3 in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 153700 , 611809 , 193220 , 613194 , 608161

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2010

Cross-species summary: This disorder has been renamed in OMIA on the basis of the review by Miyadera et al. (2012)

Species-specific name: cmr3

Species-specific description: Canine multifocal retinopathy (cmr) is an ocular disorder characterized by multiple areas of retinal degeneration. The disorder detailed in this entry (cmr3) has essentially the same cinical signs as the other two forms of cmr (namely cmr1 [OMIA001553-9615] and cmr2 [OMIA001554-9615]), but as explained by Zangerl et al. (2010), the nature of the cmr3 mutation, which has been seen in only one breed (Lapponian Herder), suggests a different molecular mechanism.

Mapping: CFA18

Molecular basis: The causative mutations for Cmr3 in the Lapponian herder are a deletion and a G to T substitution in exon 10 of BEST1 (Zangerl et al., 2010).

Clinical features: Signs of cmr include multiple tan-pink subretinal patches in both the tapetal and the non-tapetal fundus along with focal areas of tapetal hyper-reflectivity. The lesions elevate the retina, progressing as the dog ages, to focal areas of retinal degeneration and retinal pigment epithelial hypertrophy and pigmentation (Grahn et al., 1998).

Pathology: In retinal histology there are multiple areas of retinal pigment epithelial vacuolation, hypertrophy, apparent separation from Bruch’s membrane, and multiple serous retinal detachments (Grahn et al., 1998).

Control: Relatives of affected dogs should be tested. Breeding of affected or carrier animals is not recommended. If carriers must be bred, it should be bred only to a tested, homozygous normal dog.

Genetic testing: There are tests available to detect the known causative mutations.

Breed: Lapponian Herder .

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
BEST1 bestrophin 1 Canis lupus familiaris 18 NC_006600.3 (54483565..54468844) BEST1 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
Lapponian Herder Multifocal retinopathy 3 BEST1 cmr3 deletion, small (<=20) c.1388delC p.Pro463fs 2010 21197113 Variant information and allele abbreviation gleaned from or confirmed by Donner et al. (2016) PLoS One 11:e0161005

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.
2013 Guziewicz, K.E., Zangerl, B., Komáromy, A.M., Iwabe, S., Chiodo, V.A., Boye, S.L., Hauswirth, W.W., Beltran, W.A., Aguirre, G.D. :
Recombinant AAV-Mediated BEST1 Transfer to the Retinal Pigment Epithelium: Analysis of Serotype-Dependent Retinal Effects. PLoS One 8:e75666, 2013. Pubmed reference: 24143172. DOI: 10.1371/journal.pone.0075666.
2012 Guziewicz, K.E., Aguirre, G.D., Zangerl, B. :
Modeling the Structural Consequences of BEST1 Missense Mutations. Adv Exp Med Biol 723:611-8, 2012. Pubmed reference: 22183385. DOI: 10.1007/978-1-4614-0631-0_78.
Miyadera, K., Acland, G.M., Aguirre, G.D. :
Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies. Mamm Genome 23:40-61, 2012. Pubmed reference: 22065099. DOI: 10.1007/s00335-011-9361-3.
2010 Zangerl, B., Wickström, K., Slavik, J., Lindauer, S.J., Ahonen, S., Schelling, C., Lohi, H., Guziewicz, K.E., Aguirre, G.D. :
Assessment of canine BEST1 variations identifies new mutations and establishes an independent bestrophinopathy model (cmr3). Mol Vis 16:2791-804, 2010. Pubmed reference: 21197113.
1998 Grahn, BH., Philibert, H., Cullen, CL., Houston, DM., Semple, HA., Schmutz, SM. :
Multifocal retinopathy of Great Pyrenees dogs. Vet Ophthalmol 1:211-221, 1998. Pubmed reference: 11397233.

Edit History


  • Created by Frank Nicholas on 04 Mar 2011
  • Changed by Vicki Meyers-Wallen on 28 Sep 2011
  • Changed by Frank Nicholas on 29 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011