In other species: American mink

Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 103500 (trait) , 156845 (gene)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: Glass-eyed albino; German White Fleckvieh syndrome

Species-specific description: Philipp et al. (2011) reported a "dominantly inherited syndrome associated with hypopigmentation, heterochromia irides, colobomatous eyes and bilateral hearing loss . . . in Fleckvieh cattle"

Mapping: Using a genome-wide scan with the bovine Illumina SNP chip, Philipp et al. (2011) mapped this disorder to a region of chromosome BTA22 identified by three SNPs located "at 33.422, 36.052 and 36.060 Mb". This regions contains 13 genes, including the gene encoding microphthalmia-associated transcription factor (MITF), a strong candidate. Using "8 cases and 4 control maternal cousins", each genotyped with the Illumina BovineSNP50 chip, Capitan et al. (2014)/Bourneuf et al. (2017) narrowed the location of this trait to a 1.6Mb region on chromosome BTA22: 31,446,714-33,076,318 that contains MITF.

Molecular basis: Philipp et al. (2011) reported the cause of this disorder in German Fleckvieh cattle as being a "missense mutation (c.629G>T, p.210R>I) was identified within exon 7 of the bovine MITF" gene. Bourneuf et al. (2017) discovered a de novo likely causal variant in the same gene in the Holstein breed, namely BTA22: g.31746506_31746508del; p.R211del (UMD3.1).

Clinical features: As described by Philipp et al. (2011): "The German White Fleckvieh cattle family exhibited pure white coat color, pink skin without any darker spots or ghost patterns, yellow-white hooves, white horns, pigmentless muzzle, anus, eyelids, eye lashes, cilia, nictitating membranes and conjunctivae . . . . The irides were pale blue in the central part and white towards the periphery . . . . Pupils exhibited typical albinotic light reflection and the ocular fundus was completely or nearly completely albinotic using direct ophthalmoscopy . . . . Optic disks were enlarged and irregular. The white animals were bilaterally deaf. We could not observe behavioural reactions or Preyer's reflex on different sounds. Sensorineural hearing loss could be confirmed using brainstem auditory evoked response (BAER) tests in two young bulls."

Breed: Fleckvieh-Simmental, Germany (Cattle) (VBO_0002354).
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: