Waardenburg Syndrome, type 2A

Gene: MITF

Transmission: Autosomal dominant

Mutation: Deletion, MITF gene; c.668_670 dél), p.R224 dél), chr.22.

Medical systems: Cutanious

Breeds: Angus

Age of onset of symptoms: From birth.

A white Angus calf was born to black Angus parents. Genomic sequencing of the three animals revealed a heterozygous de-novo mutation within the MITF gene in the calf. The MITF gene codes for a transcription factor expressed by neural crest cells during development that is important for normal pigmentation production that can also be involved in normal ear and eye development and function. The mutation identified in the calf was a 3-bp deletion at the same site that is a cause of Waarenberg syndrome type 2A in humans, a genetic disease involving pigmentation disturbances and deafness. Because of its de-novo and dominant nature, the mutation and phenotype reported for the white Angus calf is of academic interest but is not of concern to Angus breeders.

Several mutations within the MITF gene are reported in cattle that involve depigmentation phenotypes that may or may not be accompanied with deafness or microphthalmia:

MITF gene, White, Waarenburg syndrome (Angus): [OMIA 1401-9913]

MITF gene, Coat color, dominant white, deafness (Fleckvieh-Simmental, Holstein): [OMIA 1680-9913]

MITF gene, Depigmenatation, microphthalmia (Holstein): [OMIA 1931-9913]

References:

OMIA link: [1401-9913]

Petersen JL, Sieck RL, Steffen DJ. (2023). White coat color of a Black Angus calf attributed to an occurrence of the delR217 variant of MITF. Animal Genetics, 54(4):549-552. [pm/37062854]

Hofstetter S, Seefried F, Häfliger IM, et al. (2019) A non-coding regulatory variant in the 5′-region of the MITF gene is associated with white-spotted coat in Brown Swiss cattle. Animal Genetics 50(1):27-32. [pm/30506810]

Wiedemar N, Drögemüller C. (2014) A 19-Mb de novo deletion on BTA 22 including MITF leads to microphthalmia and the absence of pigmentation in a Holstein calf. Anim Genet 45(6):868-70. [pm/25199536]

Philipp U, Lupp B, Mömke S, et al. (2011) A MITF mutation associated with a dominant white phenotype and bilateral deafness in German Fleckvieh cattle. PLoS One 6:e28857. [pm/22174915]

Contributed by: Sarah Blouin and Léah Proulx, Class of 2028, Faculty of Veterinary Medicine, University of Montreal. (Translation, DWS)