OMIA 001765-9940 : Waardenburg syndrome, type 4A in Ovis aries

Possibly relevant human trait(s) and/or gene(s) (MIM number): 277580

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: Cameroon.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
EDNRB endothelin receptor type B Ovis aries 10 NC_019467.2 (53476966..53447691) EDNRB Homologene, Ensembl, NCBI gene

Variants

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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
Cameroon Waardenburg syndrome, type 4A EDNRB deletion, gross (>20) 10 "a deletion of about 110 kb on sheep chromosome [OVA]10, comprising the entire EDNRB gene" 2012 23300849

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.
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 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.
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.
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.

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