OMIA:001736-9913 : Polled and multisystemic syndrome in Bos taurus (taurine cattle)
Categories: Craniofacial phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2012
Species-specific symbol: PMS
History: This disorder was first described by Capitan et al. (2012), as a result of screening the entire French cattle population for novel horn-development abnormalities, which identified a "Charolais bull (V.), born to horned parents, that never developed normal horns but instead small horny scabs and for which the polled progeny displayed severe additional symptoms."
Inheritance: As reported by Capitan et al. (2012), "male-specific lethality during the first third of gestation" gives rise to sex-ratio distortion. The authors noted that this is "the first case of male-specific lethality associated with an autosomal locus in a non-murine mammalian species".
Mapping: Capitan et al. (2012) conducted a genome scan with a 50,000 SNP chip on the proband Charolais bull V, "19 unaffected progeny, three affected daughters and their dams". This highlighted a 2.8Mb region on chromosome BTA2 which showed a cluster of loci showing errors of Mendelian inheritance, suggestive of a deletion.
Molecular basis: Genotyping of the three affected daughters with a 777,000 SNP chip, combined with whole-genome sequencing of one of the affected daughters, enabled Capitan et al. (2012) to identify the causative mutation as a 3.7Mb deletion encompassing the genes ARHGAP15, GTDC1 and ZEB2. Comparison with the homologous human disorder (see MIM entry above) implied that the syndrome is primarily due to the deletion of ZEB2.
Gerhke et al. (2020) identified "an 11-bp deletion (AC_000159.1:g.52364063_52364073del; Del11) in the second exon of ZEB2 gene as the causal mutation for . . .[a] de novo polled condition [in a "polled bull (FV-Polled1) born to horned parents, indicating a de novo origin of this polled condition"]. We predicted that the deletion would shorten the protein product of ZEB2 by almost 91%. Moreover, we showed that all animals carrying Del11 mutation displayed symptoms similar to Mowat-Wilson syndrome (MWS) in humans, which is also associated with genetic variations in ZEB2. The symptoms in cattle include delayed maturity, small body stature and abnormal shape of skull."
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: As reported by Capitan et al. (2012), this disorder's "clinical spectrum includes polledness (complete agenesis of horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, and variable neurological and cardiac anomalies".
Charolais (Cattle) (VBO_0000177),
Simmental (Cattle) (VBO_0000380).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ZEB2||zinc finger E-box binding homeobox 2||Bos taurus||-||no genomic information (-..-)||ZEB2||Homologene, Ensembl , NCBI gene|
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
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.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|921||Charolais (Cattle)||Polled and multisystemic syndrome||ZEB2||deletion, gross (>20)||Naturally occurring variant||2||A 3.7Mb deletion encompassing the genes ARHGAP15, GTDC1 and ZEB2||2012||23152852|
|1246||Simmental (Cattle)||Polledness, abnormal skull shape, small body stature and subfertility||ZEB2||Del11||deletion, small (<=20)||Naturally occurring variant||ARS-UCD1.2||2||g.52263360_52263370del||2020||33046754|
Cite this entry
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.
|2020||Gehrke, L.J., Upadhyay, M., Heidrich, K., Kunz, E., Klaus-Halla, D., Weber, F., Zerbe, H., Seichter, D., Graf, A., Krebs, S., Blum, H., Capitan, A., Thaller, G., Medugorac, I. :|
|A de novo frameshift mutation in ZEB2 causes polledness, abnormal skull shape, small body stature and subfertility in Fleckvieh cattle. Sci Rep 10:17032, 2020. Pubmed reference: 33046754. DOI: 10.1038/s41598-020-73807-5.|
|2012||Capitan, A., Allais-Bonnet, A., Pinton, A., Marquant-Le Guienne, B., Le Bourhis, D., Grohs, C., Bouet, S., Clément, L., Salas-Cortes, L., Venot, E., Chaffaux, S., Weiss, B., Delpeuch, A., Noé, G., Rossignol, M.N., Barbey, S., Dozias, D., Cobo, E., Barasc, H., Auguste, A., Pannetier, M., Deloche, M.C., Lhuilier, E., Bouchez, O., Esquerré, D., Salin, G., Klopp, C., Donnadieu, C., Chantry-Darmon, C., Hayes, H., Gallard, Y., Ponsart, C., Boichard, D., Pailhoux, E. :|
|A 3.7 Mb deletion encompassing ZEB2 causes a novel polled and multisystemic syndrome in the progeny of a somatic mosaic bull. PLoS One 7:e49084, 2012. Pubmed reference: 23152852. DOI: 10.1371/journal.pone.0049084.|
- Created by Frank Nicholas on 23 Nov 2012
- Changed by Frank Nicholas on 23 Nov 2012
- Changed by Frank Nicholas on 21 Oct 2020
- Changed by Imke Tammen2 on 22 May 2022