{"id":23856,"date":"2025-04-22T14:24:57","date_gmt":"2025-04-22T14:24:57","guid":{"rendered":"https:\/\/labgenvet.ca\/?page_id=23856"},"modified":"2025-04-22T14:26:09","modified_gmt":"2025-04-22T14:26:09","slug":"auditory-pigmentary-syndrome-pax3-related","status":"publish","type":"page","link":"https:\/\/labgenvet.ca\/en\/auditory-pigmentary-syndrome-pax3-related\/","title":{"rendered":"Auditory-pigmentary syndrome, PAX3 -related"},"content":{"rendered":"

Auditory-pigmentary syndrome, PAX3 -related<\/strong><\/h1>\n

 <\/p>\n

Gene<\/strong>:\u00a0PAX3<\/p>\n

Transmission<\/strong>: Autosomal, dominant (incomplete)<\/p>\n

The animal only has to have one copy of the mutation to be at risk of developing hypertrophic cardiomyopathy. \u00a0Animals 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. \u00a0Offspring are potentially at risk of developing the disease if at least one parent carries the mutation.\u00a0 Alternatively, the disease is caused by a de novo mutation.<\/p>\n

Mutations<\/strong>:<\/p>\n

Mutation Splashed White 2 (SW2): Substitution, PAX3 gene; c.209 G>A, p.(Cys70Tyr), chromosome 6.<\/p>\n

Mutation Splashed White 4 (SW4): Substitution, PAX3 gene; c.95 C>G, p.(Pro32Arg), chromosome 6.<\/p>\n

Mutation Splashed White 10 (SW10): Substitution (nonsense), PAX3 gene; c.583 C>T, p.(Arg195 STOP), chromosome 6.<\/p>\n

Breeds<\/strong>: American Paint, Appaloosa (SW4), Lipizzan (SW2), Noriker (SW2), Purebred Spanish (SW10), Quarter Horse (SW2).<\/p>\n

Medical system:<\/strong>\u00a0Deafness, dermal (pigmentation)<\/p>\n

Age of onset of symptoms<\/strong>: From birth.<\/p>\n

Horses are noted for their wide variety of white spotting phenotypes, ranging from isolated small white spots to a completely white horse. \u00a0Melanocytes are the mature cells responsible for pigment production in the skin.\u00a0 They are derived developmentally from a population of embryonic cells called neural crest cells.\u00a0 Mutations in a large group of genes (EDNRB, KIT, MITF, PAX3, TRPM1, RFWD3 and HPS5) can cause a failure of neural crest cells to survive or migrate properly during embryogenesis, resulting in regional lack of melanocytes in the skin and thus in white spotting. Neural crest cells also contribute to other cell populations, and some of the mutations that give white spotting can be involved in additional phenotypes including deafness, ocular problems, intestinal problems, infertility and indeed embryo lethality.\u00a0 For example, the presence of melanocytes within the stria vascularis of the cochlear duct is important for proper hearing.<\/p>\n

The Splashed White (SW) phenotypes in the horse are a white spotting pattern characterized by white legs and belly as if the animal had been dipped or splashed in white paint.\u00a0 Mutations in two genes, PAX3 and MITF, can be responsible for the SW phenotypes.\u00a0 Both PAX3 and MITF genes code for transcription factors important for neural crest cell migration and survival; indeed, the product of the PAX3 gene is important for the expression of the MITF gene.\u00a0 Mutations in either PAX3 or MITF can be associated with deafness.\u00a0 Three mutations in the PAX3 gene are associated with splashed white markings and with blue eyes when heterozygous.\u00a0 One copy of the SW2 mutation is known to be associated with deafness with variable penetration, while two copies can give a completely white animal.\u00a0 The SW4 and SW10 PAX3 mutations may be embryo lethal when homozygous. Slashed White pigmentation patterns caused by MITF mutations (SW1, SW3, SW5, SW6, SW7, SW8) are also associated with deafness.<\/p>\n

Veterinarians and breeders should be aware of the possible health associations with the Splashed White phenotypes.\u00a0 More studies are warranted.\u00a0 DNA tests are available for the different SW mutations.<\/p>\n

 <\/p>\n

References:<\/strong><\/p>\n

OMIA link: [1688-9796<\/a>], [0214-9796<\/a>]<\/p>\n

Durward-Akhurst SA, Marlowe JL, Schaefer RJ, et al. (2024<\/strong>) Predicted genetic burden and frequency of phenotype-associated variants in the horse.\u00a0Sci Rep\u00a014:8396.\u00a0 [pm\/38600096<\/a>]<\/p>\n

McFadden A, Vierra M, Martin K, et al. (2024<\/strong>) Spotting the pattern: A review on white coat color in the domestic horse.\u00a0Animals (Basel)\u00a014:451.\u00a0 [pm\/38338094<\/a>]<\/p>\n

McFadden A, Martin K, Foster G, et al. (2023<\/strong>) Two novel variants in MITF and PAX3 associated with splashed white phenotypes in horses.\u00a0J Equine Vet Sci\u00a0128:104875.\u00a0 [pm\/37406837<\/a>]<\/p>\n

Druml T, Grilz-Seger G, Neuditschko M, et al. (2018<\/strong>) Novel insights into Sabino1 and splashed white coat color patterns in horses.\u00a0Anim Genet\u00a049:249-253.\u00a0 [pm\/29635692<\/a>]<\/p>\n

D\u00fcrig N, Jude R, Jagannathan V, Leeb T. (2017<\/strong>) A novel MITF variant in a white American Standardbred foal.\u00a0Anim Genet\u00a048:123-124, 2017.\u00a0 [pm\/27592871<\/a>]<\/p>\n

Hauswirth R, Haase B, Blatter M, et al. (2012<\/strong>) Mutations in MITF and PAX3 cause “splashed white” and other white spotting phenotypes in horses.\u00a0PLoS Genet\u00a08(4):e1002653. [pm\/22511888<\/a>]<\/p>\n

Magdesian KG, Williams DC, Aleman M, et al. (2009<\/strong>) Evaluation of deafness in American Paint Horses by phenotype, brainstem auditory-evoked responses, and endothelin receptor B genotype.\u00a0J Am Vet Med Assoc\u00a0235:1204-11.\u00a0 [pm\/19912043<\/a>]<\/p>\n

 <\/p>\n

Contributed by: Me\u0301lody Nault and Julie-Pier Rousseland, Class of 2029, Facult\u00e9 de m\u00e9decine v\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al.\u00a0 (Translation DWS)<\/p>\n","protected":false},"excerpt":{"rendered":"

Auditory-pigmentary syndrome, PAX3 -related   Gene:\u00a0PAX3 Transmission: Autosomal, dominant (incomplete) The animal only has to have one copy of the mutation to be at risk of developing hypertrophic cardiomyopathy. \u00a0Animals 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…<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-23856","page","type-page","status-publish","hentry","description-off"],"acf":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/pages\/23856","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/comments?post=23856"}],"version-history":[{"count":2,"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/pages\/23856\/revisions"}],"predecessor-version":[{"id":23858,"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/pages\/23856\/revisions\/23858"}],"wp:attachment":[{"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/media?parent=23856"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}