--- license: permission_granted topic_id: companion_breed_health_border_collie_omia3472_dog category: companion-breed-health title: "Border Collie — Intestinal cobalamin (vitamin B12) malabsorption, CUBN-related (hereditary; OMIA-verified breed predisposition)" lang: en source: "OMIA (Online Mendelian Inheritance in Animals, University of Sydney) breed-specific hereditary-disorder record, saved verbatim to source_file; C1 substring-verified. Pulled 2026-08-02 from local OMIA database dump." source_file: pdf-raw/breed-health/border_collie_omia3472_3472.txt date_parsed: 2026-08-02 tokens_estimated: 685 verification: method: substring_match claims: 9 passed: 9 date: 2026-08-02 recovered: false path: companion-breed-health/companion_breed_health_border_collie_omia3472_dog/01_companion_breed_health_border_collie_omia3472_dog.md source_document: "OMIA — Online Mendelian Inheritance in Animals (University of Sydney)" citation: authority: "OMIA — Online Mendelian Inheritance in Animals (University of Sydney)" title: "Border Collie — Intestinal cobalamin (vitamin B12) malabsorption, CUBN-related (hereditary; OMIA-verified breed predisposition)" url: "https://omia.org/OMIA001786/9615/" retrieved: "2026-08-02" ref: "OMIA breed-specific hereditary-disorder records (omia.org), derived from local OMIA database dump; dataset: https://doi.org/10.25910/2AMR-PV70" doc_type: "academic animal-genetics database (breed-specific disorder entries)" needs_review: false
Border Collie — Intestinal cobalamin (vitamin B12) malabsorption, CUBN-related (hereditary; OMIA-verified breed predisposition)
Source: first-hand OMIA (University of Sydney) breed-specific hereditary-disorder record, saved verbatim to source_file; every claim below is a C1 byte-substring of it.
Claims
Breed: Border Collie (Dog)Disorder:Mode of inheritance: Autosomal recessiveSummary: Intestinal cobalamin malabsorption is a metabolic disorder characterized by failure to thrive, neutropenia, decreased serum cobalamin (Cbl), and nonregenerative anemia. Other signs include chronic inappetance, megaloblastic changes of the bone marrow, methylmalonic aciduria, and homocysteinemia. This phenotype can be caused by either mutations in the AMN or CUBN genes (locus heterogeneity). See also a href=../../../../../../OMIA001791/9615/OMIA:001791-9615/a. Adapted from the corresponding entry by John Fyfe in [a href=../../../../../../OMIA000565/9615/OMIA:000565-9615/a].Clin feat: Signs begin around 6 to 12 weeks of age, and include failure to thrive and chronic inappetance. Affected animals also demonstrate neutropenia with hypersegmentation, nonregenerative anemia with anisocytosis and poikilocytosis, megaloblastic changes of the bone marrow, decreased serum Cbl concentrations, methylmalonic aciduria, and homocysteinemia. These animals have normal renal function, but low-molecular weight urinary protein excretion (Fyfe et al., 1991).Defect: yesPathology: In normal dogs, Cbl is ingested in the diet and binds to intrinsic factor, a glycoprotein made by the gastric mucosa and the pancreatic duct epithelium. The complex of intrinsic factor (IF) and Cbl is absorbed through binding receptors on enterocytes in the distal jejunum and ileum. Signs of intestinal cobalamin malabsorption are due to absence of receptors for the IF-Cbl complex at the brush border (Fyfe et al., 1991). Dogs are born with cobalamin stores, but they are rapidly used up during postnatal growth unless replaced from the diet. This is when signs become apparent (Fyfe et al., 1991).Prevalence: At the time of mutation discovery Owczarek-Lipska et al. (2013) estimated the carrier frequency of the CUBN:c.8392delC defect at 6% in a cohort of 203 European Border Collies. Drögemüller et al. (2014) estimated the carrier frequency of the Beagle mutation (c.786delC) to be 9%. Mizukami et al. (2016) reported the frequency of the c.8392delC allele as 0.015 in 500 Border collies in Japan. Fyfe et al. (2018): A population study using a simple allele-specific DNA test indicated mutant allele frequencies of 8.3 and 4.5% among North American and Hungarian Komondors, respectively.Gen test: Genetic testing for the causative mutation is available. Genetic testing is recommended to confirm the clinical diagnosis in suspected cases. Genetic testing is also recommended for breeding animals to avoid the accidental mating of two carriers, which might lead to affected offspring.
Associated gene(s)
Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.
- Gene: Entrez Gene ID 388199252 (no symbol in OMIA GeneSynonym) — OMIA Phene_Gene
- OMIA molecular-genetics note: Whole genome re-sequencing of one affected Border Collie revealed 17 non-synonymous variants in the critical interval. Two of these variants were perfectly associated with intestinal cobalamin malabsorption in Border Collies. Based on the known functions of the corresponding genes the CUBN:c.8392delC frameshift variant is most likely causative for intestinal cobalamin malabsorption in Border Colli…
Evidence (references)
Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.
- 1991. Inherited Selective Intestinal Cobalamin Malabsorption and Cobalamin Deficiency in Dogs. Pediatric Research — PubMed:PMID1848001 — OMIA Phene_Article / Article
- 1991. Defective Brush-Border Expression of Intrinsic Factor- Cobalamin Receptor in Canine Inherited Intestinal Cobalamin Malabsorption. Journal of Biological Chemistry — PubMed:PMID1999430 — OMIA Phene_Article / Article
- 1999. Cobalamin deficiency associated with erythroblastic anemia and methylmalonic aciduria in a border collie. J Am Anim Hosp Assoc — PubMed:PMID10493414 | DOI:10.5326/15473317-35-5-392 — OMIA Phene_Article / Article
- 2000. Persistent cobalamin deficiency causing failure to thrive in a juvenile beagle. Journal of Small Animal Practice — PubMed:PMID11023127 — OMIA Phene_Article / Article
- 2005. Hyperammonaemic encephalopathy secondary to selective cobalamin deficiency in a juvenile Border collie. J Small Anim Pract — PubMed:PMID16035451 | DOI:10.1111/j.1748-5827.2005.tb00330.x — OMIA Phene_Article / Article
- 2003. Canine Imerslund-Grasbeck syndrome maps to a region orthologous to HSA14q. Mamm Genome — PubMed:PMID14722725 | DOI:10.1007/s00335-003-2280-1 — OMIA Phene_Article / Article
- 1991. Role of the pancreas in the absorption and malabsorption of cobalamin (vitamin B-12) in dogs. J Nutr — PubMed:PMID1941244 — OMIA Phene_Article / Article
- 2004. The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood — PubMed:PMID14576052 | DOI:10.1182/blood-2003-08-2852 — OMIA Phene_Article / Article
- 2005. Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo. Blood — PubMed:PMID15845892 | DOI:10.1182/blood-2005-03-1197 — OMIA Phene_Article / Article
- 2013. A frameshift mutation in the cubilin gene (CUBN) in Border Collies with Imerslund-Gräsbeck syndrome (selective cobalamin malabsorption). PLoS One — PubMed:PMID23613799 | DOI:10.1371/journal.pone.0061144 — OMIA Phene_Article / Article
- 2013. Clinical and laboratory findings in border collies with presumed hereditary juvenile cobalamin deficiency. J Am Anim Hosp Assoc — PubMed:PMID23535754 | DOI:10.5326/JAAHA-MS-5867 — OMIA Phene_Article / Article
- 1996. Hereditary cobalamin deficiency in border collie dogs. Journal of Veterinary Internal Medicine — OMIA Phene_Article / Article
- (12 additional references in OMIA)
Comparative medicine (human OMIM)
Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.
- OMIM:261100 (type: trait) — OMIA Group_OMIM (via OMIA_ID)
- OMIM:602997 (type: gene) — OMIA Group_OMIM (via OMIA_ID)
verification_derived: method: derived_from_dataset source: "OMIA database dump (omia.xml, local); fields Gene/Variant/Article/OMIM" note: "Structured fields (gene, variant rsID/protein change, PubMed/DOI references, OMIM cross-link) extracted from OMIA dump and presented with first-hand values; not verbatim prose."