OMIA 001680-9913 : Dominant white with bilateral deafness in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 103500

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: 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: German Fleckvieh.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MITF microphthalmia-associated transcription factor Bos taurus 22 NC_037349.1 (31843514..31614654) MITF Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
German Fleckvieh Dominant white with bilateral deafness MITF missense UMD3.1 22 g.31746502G>T c.629G>T p.R210I 2011 22174915 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
Holstein Glass-eyed albino MITF deletion, small (<=20) UMD3.1 22 g.31746506_31746508del p.R211del 2017 28904385

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2017 Bourneuf, E., Otz, P., Pausch, H., Jagannathan, V., Michot, P., Grohs, C., Piton, G., Ammermüller, S., Deloche, M.C., Fritz, S., Leclerc, H., Péchoux, C., Boukadiri, A., Hozé, C., Saintilan, R., Créchet, F., Mosca, M., Segelke, D., Guillaume, F., Bouet, S., Baur, A., Vasilescu, A., Genestout, L., Thomas, A., Allais-Bonnet, A., Rocha, D., Colle, M.A., Klopp, C., Esquerré, D., Wurmser, C., Flisikowski, K., Schwarzenbacher, H., Burgstaller, J., Brügmann, M., Dietschi, E., Rudolph, N., Freick, M., Barbey, S., Fayolle, G., Danchin-Burge, C., Schibler, L., Bed'Hom, B., Hayes, B.J., Daetwyler, H.D., Fries, R., Boichard, D., Pin, D., Drögemüller, C., Capitan, A. :
Rapid Discovery of De Novo Deleterious Mutations in Cattle Enhances the Value of Livestock as Model Species. Sci Rep 7:11466, 2017. Pubmed reference: 28904385. DOI: 10.1038/s41598-017-11523-3.
2011 Philipp, U., Lupp, B., Mömke, S., Stein, V., Tipold, A., Eule, J.C., Rehage, J., Distl, O. :
A MITF mutation associated with a dominant white phenotype and bilateral deafness in German Fleckvieh cattle. PLoS One 6:e28857, 2011. Pubmed reference: 22174915. DOI: 10.1371/journal.pone.0028857.
1966 Leipold, H.W., Huston, K. :
A herd of glass eyed albino Hereford cattle Journal of Heredity 57:179-182, 1966. Pubmed reference: 4961565.

Edit History


  • Created by Frank Nicholas on 18 Dec 2011
  • Changed by Frank Nicholas on 18 Dec 2011
  • Changed by Frank Nicholas on 19 Sep 2017