OMIA 001524-9615 : Gallbladder mucoceles in Canis lupus familiaris |
Category: Liver/biliary system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 600803 (trait) , 171060 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: unknown
Considered a defect: yes
Year key variant first reported: 2010
Species-specific symbol: GBM
Inheritance: Mealey et al. (2010) initially proposed a dominant mode of inheritance with incomplete penetrance in Shetland Sheepdogs, based on the incomplete association between a proposed likely causal variant and disease phenotype. The authors acknowledged that further research is required. In a follow up study by Cullen et al. (2014) a multifactorial mode of inheritance as well as non-inherited etiology are discussed.
Molecular basis: Mealey et al. (2010): "An insertion (G) mutation in exon 12 of canine ABCB4 (ABCB4 1583_1584G) was found to be significantly associated with hepatobiliary disease in Shetland Sheepdogs specifically (P < 0.0001) as well as other breeds (P < 0.0006) [Cairn Terrier, Cocker Spaniel, Pomeranian]. ABCB4 1583_1584G results in a frame shift generating four stop codons that prematurely terminate ABCB4 protein synthesis within exon 12..."
However, Cullen et al. (2014) "assessed ABCB4 1583_1584G, in a wider sample of dogs with GBM compared with age and breed-matched controls. ... No statistically significant association existed between ABCB4 1583_1584G and the presence of GBM for all dogs combined or for Shetland Sheepdogs alone." The authors concluded "that clinical use of a genetic test for ABCB4 1583_1584G is premature and would not yet provide useful diagnostic information for veterinarians. It would also not provide dog breeders with information necessary to make informed breeding decisions."
Clinical features: GBM is an extrahepatic disease characterised by abnormal, intraluminal accumulation of mucus or thickened bile within the gallbladder. GBM commonly predisposes the animal to secondary gallbladder rupture, systemic infection, and extrahepatic biliary duct obstruction. Therefore, serum biochemistry often shows increased liver enzymes (AST, ALT) indicative of liver damage, hyperbilirubinemia, and leucocytosis in haematology. Common non-specific clinical signs include vomiting, lethargy, abdominal pain, anorexia, icterus, tachypnoea, polyuria-polydipsia, pyrexia, diarrhoea, and abdominal distention (Smalle, Cahalane & Köster, 2015). Chronic GBM progressing to ruptured gallbladders often present with more severe clinical signs of marked abdominal pain, jaundice, and pyrexia (Jaffey et al., 2019). [IT thanks DVM student Jonathan Haw Cherng Chee, who provided the basis of this contribution in April 2022]
Pathology: Distended gallbladder filled with mucus or bile is commonly the gross pathological findings of GBM. On the thickened inner mucosal surface of the gallbladder, GBM often presents as diffused, abundant, variably sized cystic structures filled with copious amounts of tenacious viscoelastic mucin. Histopathologically, hyperplastic tall columnar epithelial cells with abundant apical cytoplasmic mucus interspersed with scants amounts of bile within the gallbladder wall and bile duct are common (Mealey et al., 2010). [IT thanks DVM student Jonathan Haw Cherng Chee, who provided the basis of this contribution in April 2022]
Breeds: Cairn Terrier, Cocker Spaniel, Miniature Schnauzer, Pomeranian, Shetland Sheepdog.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| ABCB4 | ATP-binding cassette, sub-family B (MDR/TAP), member 4 | Canis lupus familiaris | 14 | NC_051818.1 (13379530..13307604) | ABCB4 | 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.
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 572 | Shetland Sheepdog | Gallbladder mucoceles | ABCB4 | insertion, small (<=20) | Naturally occurring variant | CanFam3.1 | 14 | g.13584928_13584929insC | c.1660_1661insG | p.(L554Rfs) | XM_539403.6; XP_539403.3; published as c.1583_1584G, the association between this variant and disease was later disproven and this variant should not be used as a diagnostic marker for GBM (Cullen et al. 2014) | 2010 | 20598156 |
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.
| 2019 | Jaffey, J.A., Pavlick, M., Webster, C.R., Moore, G.E., McDaniel, K.A., Blois, S.L., Brand, E.M., Reich, C.F., Motschenbacher, L., Hostnik, E.T., Su, D., Lidbury, J.A., Raab, O., Carr, S.V., Mabry, K.E., Fox-Alvarez, W., Townsend, S., Palermo, S., Nakazono, Y., Ohno, K., VanEerde, E., Fieten, H., Hulsman, A.H., Cooley-Lock, K., Dunning, M., Kisielewicz, C., Zoia, A., Caldin, M., Conti-Patara, A., Ross, L., Mansfield, C., Lynn, O., Claus, M.A., Watson, P.J., Swallow, A., Yool, D.A., Gommeren, K., Knops, M., Ceplecha, V., de Rooster, H., Lobetti, R., Dossin, O., Jolivet, F., Papazoglou, L.G., Pappalardo, M.C.F., Manczur, F., Dudás-Györki, Z., O'Neill, E.J., Martinez, C., Gal, A., Owen, R.L., Gunn, E., Brown, K., Harder, L.K., Griebsch, C., Anfinsen, K.P., Gron, T.K., Marchetti, V., Heilmann, R.M., Pazzi, P., DeClue, A.E. : |
| Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele. Vet J 251:105350, 2019. Pubmed reference: 31492387. DOI: 10.1016/j.tvjl.2019.105350. | |
| 2015 | Smalle, T.M., Cahalane, A.K., Köster, L.S. : |
| Gallbladder mucocoele: A review. J S Afr Vet Assoc 86:1318, 2015. Pubmed reference: 26824341. DOI: 10.4102/jsava.v86i1.1318. | |
| 2014 | Cullen, J.M., Willson, C.J., Minch, J.D., Kimbrough, C.L., Mealey, K.L. : |
| Lack of association of ABCB4 insertion mutation with gallbladder mucoceles in dogs. J Vet Diagn Invest 26:434-436, 2014. Pubmed reference: 24760133. DOI: 10.1177/1040638714532099. | |
| 2010 | Mealey, K.L., Minch, J.D., White, S.N., Snekvik, K.R., Mattoon, J.S. : |
| An insertion mutation in ABCB4 is associated with gallbladder mucocele formation in dogs. Comp Hepatol 9:6, 2010. Pubmed reference: 20598156. DOI: 10.1186/1476-5926-9-6. | |
| 2009 | Mesich, M.L., Mayhew, P.D., Paek, M., Holt, D.E., Brown, D.C. : |
| Gall bladder mucoceles and their association with endocrinopathies in dogs: a retrospective case-control study. J Small Anim Pract 50:630-5, 2009. Pubmed reference: 19954439. DOI: 10.1111/j.1748-5827.2009.00811.x. | |
| 2007 | Aguirre, A.L., Center, S.A., Randolph, J.F., Yeager, A.E., Keegan, A.M., Harvey, H.J., Erb, H.N. : |
| Gallbladder disease in Shetland Sheepdogs: 38 cases (1995-2005). J Am Vet Med Assoc 231:79-88, 2007. Pubmed reference: 17605668. DOI: 10.2460/javma.231.1.79. | |
| 2004 | Pike, F.S., Berg, J., King, N.W., Penninck, D.G., Webster, C.R. : |
| Gallbladder mucocele in dogs: 30 cases (2000-2002). J Am Vet Med Assoc 224:1615-22, 2004. Pubmed reference: 15230443. DOI: 10.2460/javma.2004.224.1615. | |
| Worley, D.R., Hottinger, H.A., Lawrence, H.J. : | |
| Surgical management of gallbladder mucoceles in dogs: 22 cases (1999-2003). J Am Vet Med Assoc 225:1418-22, 2004. Pubmed reference: 15552319. DOI: 10.2460/javma.2004.225.1418. |
Edit History
- Created by Frank Nicholas on 02 Nov 2010
- Changed by Frank Nicholas on 26 Sep 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Imke Tammen2 on 04 Feb 2022
- Changed by Imke Tammen2 on 22 May 2022