OMIA 000733-9796 : Multiple ocular defects in Equus caballus

In other species: cattle , dog , alpaca

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Co-Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: Equine Multiple Congenital Ocular Anomalies; previously known as Anterior Segment Dysgenesis or Congenital Aniridia

Species-specific symbol: MCOA

Species-specific description: This disorder is a pleiotropic effect of an allele/variant for Silver coat colour; see OMIA 001438-9796 : Coat colour, silver in Equus caballus

Mapping: Andersson et al. (2008) mapped this disorder to a 4.9 Mb region on chromsome ECA6q containing the PMEL17 gene, an exon 11 missense mutation in which causes Silver coat colour (OMIA001438-9796). Furthermore, they reported that the actual missense mutation showed complete linkage with the disorder. The candidate region was narrowed to a 208kb region by Andersson, Lyberg et al. (2011).

Molecular basis: From studying the exon 11 missense Silver mutation in PMEL17 (OMIA001438-9796) in five affected ponies, Komáromy et al. (2011) concluded "Our case series supports the notion that the (still unknown) MCOA [mutation] and the PMEL17 (Silver) [mutation] are the same, or at least overlap on ECA6q23".

A month later, Andersson, Axelsson et al. (2011) confirmed the above result, by showing that in Icelandic horses the disorder segregates with the missense mutation in exon 11 of PMEL17 (Arg618Cys) that causes Silver coat colour (OMIA001438-9796), but they did report three horses heterozygous for the PMEL17 mutation that did not show any clinical signs, suggesting incomplete penetrance.

Andersson et al. (2013) deep-sequenced the 208kb candidate region (see Mapping section above) in "five homozygous MCOA horses from three different breeds [American Miniature, Icelandic Horse, Rocky Mountain Horse], one horse with the heterozygous Cyst phenotype [American Miniature] and four unaffected controls [American Miniature, Rocky Mountain Horse]". After excluding all SNPs and indels that did not exactly match the inheritance of the disorder in the ten sequenced horses, only two SNPs remained, both in what they called the PMEL gene (one in a nonconserved intronic region, and the other a missence mutation (Arg625Cys), which is actually the same as the silver mutation (Arg618Cys) studied by Andersson, Axelsson et al. (2011). Andersson et al. (2013) concluded that "the missense mutation is causative and has pleiotrophic effect, causing both the horse silver coat color and MCOA syndrome".

Note that the current name for PMEL17 is PMEL.

Clinical features: As summarised by Andersson et al. (2013), "Horses with the MCOA phenotype are homozygous for the disease allele and have a wide range of eye anomalies . . . . These include, but are not restricted to, uveal cysts, cornea globosa, iris stromal hypoplasia, abnormal pectinate ligaments, cataracts and iris hypoplasia . . . . Horses that are heterozygous for the disease causing allele have the less severe Cyst phenotype which mainly consists of cysts that originate from the temporal ciliary body, iris, and/or extend into the temporal, peripheral retina"

Breeds: Icelandic, Kentucky Mountain Saddle, Rocky Mountain.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
PMEL premelanosome protein Equus caballus 6 NC_009149.3 (74578149..74569524) PMEL Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
American Miniature Horse Icelandic Rocky Mountain Coat colour, silver AND Multiple congenital ocular anomalies PMEL missense g.73665304C>T p.R625C 2006 17029645

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.
2017 Bellone, R.R. :
Genetic Testing as a Tool to Identify Horses with or at Risk for Ocular Disorders. Vet Clin North Am Equine Pract 33:627-645, 2017. Pubmed reference: 29103563. DOI: 10.1016/j.cveq.2017.08.005.
2013 Andersson, L.S., Wilbe, M., Viluma, A., Cothran, G., Ekesten, B., Ewart, S., Lindgren, G. :
Equine Multiple Congenital Ocular Anomalies and Silver Coat Colour Result from the Pleiotropic Effects of Mutant PMEL. PLoS One 8:e75639, 2013. Pubmed reference: 24086599. DOI: 10.1371/journal.pone.0075639.
Ségard, E.M., Depecker, M.C., Lang, J., Gemperli, A., Cadoré, J.L. :
Ultrasonographic features of PMEL17 (Silver) mutant gene-associated multiple congenital ocular anomalies (MCOA) in Comtois and Rocky Mountain horses. Vet Ophthalmol :, 2013. Pubmed reference: 23278951. DOI: 10.1111/vop.12021.
2011 Andersson, LS., Axelsson, J., Dubielzig, RR., Lindgren, G., Ekesten, B. :
Multiple Congenital Ocular Anomalies in Icelandic horses. BMC Vet Res 7:21, 2011. Pubmed reference: 21615885. DOI: 10.1186/1746-6148-7-21.
Andersson, LS., Lyberg, K., Cothran, G., Ramsey, DT., Juras, R., Mikko, S., Ekesten, B., Ewart, S., Lindgren, G. :
Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases. Mamm Genome 22:353-60, 2011. Pubmed reference: 21465164. DOI: 10.1007/s00335-011-9325-7.
Komáromy, A.M., Rowlan, J.S., La Croix, N.C., Mangan, B.G. :
Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome in PMEL17 (Silver) mutant ponies: five cases. Vet Ophthalmol 14:313-20, 2011. Pubmed reference: 21929608. DOI: 10.1111/j.1463-5224.2011.00878.x.
2008 Andersson, L.S., Juras, R., Ramsey, D.T., Eason-Butler, J., Ewart, S., Cothran, G., Lindgren, G. :
Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on horse chromosome 6. BMC Genet 9:88, 2008. Pubmed reference: 19099555. DOI: 10.1186/1471-2156-9-88.
Grahn, BH., Pinard, C., Archer, S., Bellone, R., Forsyth, G., Sandmeyer, LS. :
Congenital ocular anomalies in purebred and crossbred Rocky and Kentucky Mountain horses in Canada. Can Vet J 49:675-81, 2008. Pubmed reference: 19412389.
2006 Brunberg, E., Andersson, L., Cothran, G., Sandberg, K., Mikko, S., Lindgren, G. :
A missense mutation in PMEL17 is associated with the Silver coat color in the horse. BMC Genetics 7:46, 2006. Pubmed reference: 17029645. DOI: 10.1186/1471-2156-7-46.
2000 Ewart, S.L., Ramsey, D.T., Xu, J., Meyers, D. :
The horse homolog of congenital aniridia conforms to codominant inheritance Journal of Heredity 91:93-98, 2000. Pubmed reference: 10768120.
1999 Ramsey, DT., Ewart, SL., Render, JA., Cook, CS., Latimer, CA. :
Congenital ocular abnormalities of Rocky Mountain Horses. Vet Ophthalmol 2:47-59, 1999. Pubmed reference: 11397242.
1996 Gobel, H., Koene, M. :
Bilateral multiple congenital ocular defects in a standardbred foal [German] Pferdeheilkunde 12:3-5, 1996.

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