OMIA 001765-9940 : Waardenburg syndrome, type 4A in Ovis aries
Category: Pigmentation phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2012
Species-specific name: Familiar Hypopigmentation Syndrome; Lethal White Syndrome
Mapping: Pauciullo et al. (2013) physically mapped the ovine EDNRB gene to chromosome OAR10q22, using "R-banding and propidium iodide-staining fluorescent in situ hybridization". This confirmed the initial mapping of the same gene by Iannuzzi et al. (2001).
Molecular basis: Using a comparative-candidate gene approach (based on similar clinical signs in humans, rats and horses), Lühken et al. (2012) reported "a deletion of about 110 kb on sheep chromosome [OVA]10, comprising the entire EDNRB gene" as being responsible for this disorder. Interestingly, they noted that this region corresponds to a fragile site in the ovine genome (see OMIA 000392-9940). Pauciullo et al. (2013) confirmed the result of Lühken et al. (2012), and showed that the EDNRB gene itself is approximately 21kb in length.
Clinical features: As reported by Lühken et al. (2012), "Two of the hypopigmented lambs were available for post-mortem examination. Instead of the common brown phenotype of Cameroon sheep . . . , one of the lambs was totally white, whereas the other was also white but had pigmented distal limb ends including the claws and black marks in a small perianal area . . . . In both lambs, the irides were coloured light blue . . . , instead of dark brown as it is usual for Cameroon sheep. Both showed a considerably dilated cecum . . . and remaining meconium. Histopathological examination of intestinal samples of both lambs revealed a normal number and distribution of ganglion cells which showed a homogenous faint labelling for synaptophysin by immunohistological investigation." To the extent that the "number and distribution of ganglion cells" are normal, this disorder is more akin to Waardenberg syndrome types 1 or 2. However, Pauciullo et al. (2013) state that this ovine disorder comprises a "hypopigmented phenotype and signs of intestinal obstruction similar to aganglionosis reminiscent of the LWFS [lethal white foal syndrome]". In other words, this ovine disorder is more akin to Waardenberg syndrome 4A, which comprises hypopigmentation and Hirschprung's disease (megacolon). Variability in the extent of colonic aganglionosis is also seen in rats affected with the homologous disorder (Lühken et al., 2012).
Breed: West African Dwarf (Sheep) (VBO_0001682).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|EDNRB||endothelin receptor type B||Ovis aries||10||NC_056063.1 (53652245..53622505)||EDNRB||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 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.
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|
|930||West African Dwarf (Sheep)||Waardenburg syndrome, type 4A||EDNRB||deletion, gross (>20)||Naturally occurring variant||Oar_rambouillet_v1.0||10||"a deletion of about 110 kb on sheep chromosome [OAR]10, comprising the entire EDNRB gene"||2012||23300849|
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.
|2013||Pauciullo, A., Fleck, K., Lühken, G., Di Berardino, D., Erhardt, G. :|
|Dual-color high-resolution fiber-FISH analysis on lethal white syndrome carriers in sheep. Cytogenet Genome Res 140:46-54, 2013. Pubmed reference: 23635529. DOI: 10.1159/000350786.|
|2012||Lühken, G., Fleck, K., Pauciullo, A., Huisinga, M., Erhardt, G. :|
|Familiar hypopigmentation syndrome in sheep associated with homozygous deletion of the entire endothelin type-B receptor gene. PLoS One 7:e53020, 2012. Pubmed reference: 23300849. DOI: 10.1371/journal.pone.0053020.|
|2001||Iannuzzi, L., Di Meo, G.P., Perucatti, A., Schibler, L., Incarnato, D., Cribiu, E.P. :|
|Comparative FISH mapping in river buffalo and sheep chromosomes: assignment of forty autosomal type I loci from sixteen human chromosomes. Cytogenet Cell Genet 94:43-8, 2001. Pubmed reference: 11701953. DOI: 48781.|
|1993||Groenewald, H.B. :|
|Ultrastructure of the Epithelium of the Rumen, Reticulum and Omasum of Grey, White and Black Karakul Lambs Onderstepoort Journal of Veterinary Research 60:197-204, 1993. Pubmed reference: 7970575.|
|Groenewald, H.B. :|
|Ultrastructure of the Myenteric Ganglia in the Rumen, Reticulum, Omasum and Abomasum of Grey, White and Black Karakul Lambs Onderstepoort Journal of Veterinary Research 60:189-195, 1993. Pubmed reference: 7970574.|
|1992||Groenewald, H.B. :|
|Scanning electron microscopy of the mucosal surface of the forestomachs and abomasa of grey, white and black Karakul lambs Onderstepoort Journal of Veterinary Research 59:167-174, 1992. Pubmed reference: 1437018.|
|Groenewald, H.B., Booth, K.K. :|
|A comparative study of the thickness of the tunica muscularis in the forestomach and abomasum of grey, white and black Karakul lambs Onderstepoort Journal of Veterinary Research 59:167-174, 1992. Pubmed reference: 1437027.|
|1967||Nell, J.A. :|
|Genetic studies in Karakul sheep Annale Universiteit Van Stellenbosch 42:1-317, 1967.|
- Created by Frank Nicholas on 12 Jan 2013
- Changed by Frank Nicholas on 12 Jan 2013
- Changed by Frank Nicholas on 15 Jan 2013
- Changed by Frank Nicholas on 17 Jan 2013
- Changed by Frank Nicholas on 19 Jun 2013
- Changed by Frank Nicholas on 27 Aug 2013
- Changed by Frank Nicholas on 12 Dec 2017
- Changed by Frank Nicholas on 29 Jan 2018