OMIA:002755-9940 : Hyperbilirubinaemia, SLCO1B3-related in Ovis aries (sheep)
Categories: Liver/biliary system phene
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2018
Cross-species summary: in humans called 'Hyperbilirubinemia, Rotor type, digenic' or 'Rotor syndrome'
Species-specific name: Congenital photosensitivity and hyperbilirubinaemia
Species-specific description: A recessive disease characterized by congenital photosensitivity and hyperbilirubinaemia has been described in Southdown sheep in New Zealand (Cunningham et al., 1942) and the USA (Cornelius and Gronwall, 1968). Cornelius (1970) proposed that the disease is similar to Gilbert syndrome (listed in OMIA as OMIA:000496-9940 : Hyperbilirubinaemia I in Ovis aries), but identification of the causal variant by Posberg et al. (2018) identified that these sheep are a model for human Rotor syndrome. References relating to the disease have been moved from OMIA:000496-9940 to this entry [19/08/2023].
Inheritance: Breeding trials in New Zealand Southdown sheep revealed a recessive mode of inheritance (Hancock, 1950).
Molecular basis: Posberg et al. (2018) investigated "the genetic cause for congenital photosensitivity and hyperbilirubinemia (CPH) in Southdown sheep. ... Whole-genome sequencing was performed for a phenotypically normal Southdown sheep heterozygous for CPH. ... A nonsynonymous mutation at ovine Chr3:193,691,195, which generated a glycine-to-arginine amino acid change within the predicted Slco1b3 protein, was significantly associated with hyperbilirubinemia and predicted to be deleterious."
Clinical features: The primary clinical sign is photosensitive facial dermatitis, due to the associated defect in liver uptake of phyllorerythrin. Signs first appear at around 6-8 weeks of age, when lambs begin to eat grass. If not protected from sunlight, affected lambs develop severe dermatitis, mostly around the face and ears, which becomes infected, and eventually sloughs. Death (usually with 2-3 weeks) is a result of starvation and exhaustion (Hancock, 1950). If the lambs are protected from sunlight, they eventually die within five years, from renal failure (Cuppage et al., 1979). The cause of this renal dysfunction is not known. [Researched by Philippa Beard]
Pathology: Post-mortem reveals green and yellow discolouration of tissues, testicular atrophy, renal fibrosis, and pulmonary oedema and ascites. No gross hepatic lesions are evident. The only remarkable histopathological finding is lipofuscin accumulation in hepatocytes (McGavin, 1972). The absence of gross structural liver abnormalities helps differentiate this disorder from other forms of secondary hepatic photosensitisation, such as facial eczema. [Researched by Philippa Beard]
South Down (Sheep) (VBO_0001611).
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|
|SLCO1B3||solute carrier organic anion transporter family member 1B3||Ovis aries||3||NC_056056.1 (194556139..194480772)||SLCO1B3||Homologene, Ensembl , NCBI gene|
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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|
|1608||South Down (Sheep)||Congenital photosensitivity and hyperbilirubinaemia||SLCO1B3||missense||Naturally occurring variant||Oar_v3.1||3||g.193691915C>T||c.1318G>A||p.(G440R)||XM_012175224.1; XP_012030614.1||2018||29688779|
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.
|2018||Posbergh, C.J., Kalla, S.E., Sutter, N.B., Tennant, B.C., Huson, H.J. :|
|Mutation responsible for congenital photosensitivity and hyperbilirubinemia in Southdown sheep. Am J Vet Res 79:538-545, 2018. Pubmed reference: 29688779 . DOI: 10.2460/ajvr.79.5.538.|
|1979||Cuppage, F.E., Shimamura, T., McGavin, M.D. :|
|Nephron obstruction in mutant Southdown sheep Veterinary Pathology 16:483-485, 1979. Pubmed reference: 452323 .|
|Cuppage, F.W., McGavin, M.D., Strafuss, A.C. :|
|Animal model of human disease: intrarenal obstructive uropathy with proximal ectasia, cystic kidney disease. Am J Pathol 97:207-10, 1979. Pubmed reference: 495694 .|
|1977||Filippich, L., English, P.B. :|
|Comparison of renal function in a congenital hyperbilirubinaemia Southdown sheep and normal sheep Research in Veterinary Science 23:204-212, 1977. Pubmed reference: 928985 .|
|1975||Dhumeaux, D., Berthelot, P. :|
|Chronic hyperbilirubinaemia associated with hepatic uptake and storage impairment: a new syndrome resembling that of the mutant Southdown sheep Gastroenterology 69:988-993, 1975. Pubmed reference: 1175891 .|
|1972||McGavin, M.D., Cornelius, C.E., Gronwall, R.R. :|
|Lesions in Southdown sheep with hereditary hyperbilirubinemia Veterinary Pathology 9:142-151, 1972. Pubmed reference: 4671494 .|
|1971||Mia, A.S., Gronwall, R.R., McGavin, M.D., Cornelius, C.E. :|
|Renal function defect in mutant Southdown sheep with congenital hyperbilirubinemia. Proceedings of the Society for Experimental Biology and Medicine 137:1237-1241, 1971. Pubmed reference: 5138450 .|
|1970||Cornelius, C.E. :|
|Congenital hyperbilirubinemia. Gilbert's syndrome. Comp. Path. Bull. 2:4-5, 1970.|
|Gronwall, R.R. :|
|Sulfobromophthalein sodium excretion and hepatic storage in Corriedale and Southdown sheep with inherited hepatic dysfunction American Journal of Veterinary Research 31:2131-2133, 1970. Pubmed reference: 5505142 .|
|1969||Cornelius, C.E. :|
|Organic anion transport in mutant sheep with congenital hyperbilirubinemia Archives of Environmental Health 19:852-856, 1969. Pubmed reference: 5389192 .|
|1968||Cornelius, C.E., Gronwall, R.R. :|
|Congenital photosensitivity and hyperbilirubinemia in Southdown sheep in the United States. Am J Vet Res 29:291-5, 1968. Pubmed reference: 5754068 .|
|1952||Jamieson, N.D., Swan, J.B. :|
|Photosensitivity diseases in New Zealand. VI. Some liver function tests on congenitally photosensitive Southdown, normal Southdown and normal Romney sheep New Zealand Journal of Science and Technology 34A:354-359, 1952.|
|1950||Hancock, J. :|
|Congenital photosensitivity in Southdown sheep: a new sublethal factor in sheep New Zealand Journal of Science and Technology 32A:16-24, 1950.|
|1942||Cunningham, I.J., Hopkirk, C.S.M., Filmer, J.F. :|
|Photosensitivity diseases in New Zealand. 1. Facial eczema: its clinical, pathological, and biochemical characterization. N Z J Sci Technol A 24:185–198, 1942.|
- Created by Imke Tammen2 on 19 Aug 2023
- Changed by Imke Tammen2 on 19 Aug 2023