Multiple congenital ocular anomalies (MCOA), PMEL-related

 

Gene: PMEL

Transmission: Autosomal, co-dominant (incomplete penetrance)

The animal only has to have one copy of the mutation to be at risk of developing hypertrophic cardiomyopathy.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  Offspring are potentially at risk of developing the disease if at least one parent carries the mutation.  Alternatively, the disease is caused by a de novo mutation.

Mutation: Substitution, PMEL gene; c.1849 C>T, p.(Arg618Cys), exon11, chromosome 6.

Breeds: American Miniature horse, Ardennes horse, Contois horse, Icelandic horse, Kentucky Mountain Saddle, Missouri Fox Trotter, Morgan, Rocky Mountain horse, Shetland Pony

Medical system: Ocular, dermal.

Age of onset of symptoms: At birth (congenital).

The syndrome of multiple congenital ocular anomalies (MCOA) in the horse is caused by the same mutation in the PMEL gene that is responsible for the silver/dapple phenotype.  The PMEL gene codes for a protein important for melanosome function within melanocytes.  A mutation in the PMEL gene, known as the Z locus, is responsible for the silver/dapple coat colour and displays autosomal dominant genetics in the breeds of horses that allow this pigmentation pattern. The Z locus mutation is pleiotropic as it is also responsible for the ocular defects seen with MCOA, where it now follows co-dominant genetics.  The heterozygote (carrier) animal can have mild ocular defects including cysts within the iris, ciliary body and retina, or can be asymptomatic.  The homozygous double mutant animal can have a wide range of more severe ocular defects, including cysts, cataracts, glaucoma, corneal defects and iris defects.  Breeds of horses that do not have the silver/dapple pigmentation pattern are not susceptible to MCOA.  DNA tests should be used to identify the presence of the Z locus (and the potential for MCOA) in the chestnut-colored horse, where silver/dapple pigmentation pattern is not visually evident.

Note that mutations in the PMEL gene are responsible for the merle pigmentation phenotype seen in the dog, which can also be associated with pleiotropic effects including microphthalmia and deafness.

 

References:

OMIA links: [0733-9796], [1438-9796]

Mowat FM, Iwabe S, Aguirre GD, Petersen-Jones SM. (2024) Consensus guidelines for nomenclature of companion animal inherited retinal disorders. Vet Ophthalmol 28:663-667.  [pubmed/38334230]

Herb VM, Zehetner V, Blohm O. (2021) Multiple congenital ocular anomalies in a silver coat Missouri Fox Trotter stallion. Tierarztl Prax Ausg G Grosstiere Nutztiere 49:350-354.  [pm/34666370]

Andersson LS, Wilbe M, Viluma A, et al. (2013) Equine multiple congenital ocular anomalies and silver coat colour result from the pleiotropic effects of mutant PMEL. PLoS One 8:e75639.  [pm/24086599]

Ségard EM, Depecker MC, Lang J, et al. (2013) Ultrasonographic features of PMEL17 (Silver) mutant gene-associated multiple congenital ocular anomalies (MCOA) in Comtois and Rocky Mountain horses. Vet Ophthalmol 16:429-35.  [pm/23278951]

Andersson LS, Axelsson J, Dubielzig RR, et al. (2011) Multiple Congenital Ocular Anomalies in Icelandic horses. BMC Vet Res 7:21. [pm/21615585]

Brunberg E, Andersson L, Cothran G, et al. (2006) A missense mutation in PMEL17 is associated with the Silver coat color in the horse. BMC Genetics 7:46. [pm/17029645]

Ramsey DT, Ewart SL, Render JA, et al. (1999) Congenital ocular abnormalities of Rocky Mountain Horses. Vet Ophthalmol 2:47-59.  [pm/11397242]

 

Contributed by: Sandrine Jobin and Rose Laflamme, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)