In other species: dog , taurine cattle , alpaca

Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 155550 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal co-dominant

Disease-related: 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 Horse (Horse) (VBO_0000991), Kentucky Mountain Saddle, United States of America (Horse) (VBO_0016871), Missouri Fox Trotter, Germany (Horse) (VBO_0011358), Rocky Mountain, United States of America (Horse) (VBO_0011836).
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: