{"topic_id":"companion_breed_health_cavalier_king_charles_spaniel_omia1851_dog","category":"companion-breed-health","context":"---\nlicense: permission_granted\ntopic_id: companion_breed_health_cavalier_king_charles_spaniel_omia1851_dog\ncategory: companion-breed-health\ntitle: \"Cavalier King Charles Spaniel — Renal dysplasia (hereditary; OMIA-verified breed predisposition)\"\nlang: en\nsource: \"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.\"\nsource_file: pdf-raw/breed-health/cavalier_king_charles_spaniel_omia1851_1851.txt\ndate_parsed: 2026-08-02\ntokens_estimated: 1001\nverification:\n  method: substring_match\n  claims: 5\n  passed: 5\n  date: 2026-08-02\nrecovered: false\npath: companion-breed-health/companion_breed_health_cavalier_king_charles_spaniel_omia1851_dog/01_companion_breed_health_cavalier_king_charles_spaniel_omia1851_dog.md\nsource_document: \"OMIA — Online Mendelian Inheritance in Animals (University of Sydney)\"\ncitation:\n  authority: \"OMIA — Online Mendelian Inheritance in Animals (University of Sydney)\"\n  title: \"Cavalier King Charles Spaniel — Renal dysplasia (hereditary; OMIA-verified breed predisposition)\"\n  url: \"https://omia.org/OMIA001135/9615/\"\n  retrieved: \"2026-08-02\"\n  ref: \"OMIA breed-specific hereditary-disorder records (omia.org), derived from local OMIA database dump; dataset: https://doi.org/10.25910/2AMR-PV70\"\n  doc_type: \"academic animal-genetics database (breed-specific disorder entries)\"\n  needs_review: false\n\n\n# Cavalier King Charles Spaniel — Renal dysplasia (hereditary; OMIA-verified breed predisposition)\n\nSource: 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.\n\n## Claims\n\n- `Breed: Cavalier King Charles Spaniel (Dog)`\n- `Disorder: `\n- `Mode of inheritance: From a segregation analysis, Bovee (2003) concluded that the inheritance of this disorder is autosomal dominant with incomplete penetrance in the Shih Tzu breed.`\n- `Defect: yes`\n- `Gen test: A DNA test for this disorder in a wide range of breeds is included in the OFA's list at http://www.offa.org/dna_alltest.html, which directs enquiries to DOGenes in Peterborough, Ontario, Canada (http://www.dogenes.com/), where a Renal Dysplasia Information Page states that this company has identified the causative mutation that is the basis of the DNA test. As indicated on the DOGenes website, the basis for this claim are the results of Whiteley et al. (2011), who reported an association between the disorder (variously defined) and the presence of one or more of three mutant alleles of the COX-2 gene (officially known as PTGS2, which encodes prostaglandin-endoperoxide synthase 2; also known as prostaglandin G/H synthase or cyclooxygenase). The three alleles are characterised by small insertions or deletions a short distance upstream of the translation initiation codon of the gene. Unfortunately, the results presented by Whiteley et al. (2011) do not appear to justify the conclusions drawn: the criteria for affected were not defined sufficiently for any other researcher to conduct a comparable study; association analyses were conducted on family data while ignoring the family structure; the analyses were conducted on combined genotype data for whatever mutant alleles happened to exist in the available dogs, without any attempt to conduct separate analyses for individual mutant alleles; no segregation analysis was undertaken of the family data to provide insights into the form of inheritance of the disorder; and an across-breed analysis that involved only affected dogs (determined in a number of different manners, many not fully explained) led to the following conclusions, which speak for themselves: No dogs affected with renal dysplasia were identified with a homozygous wild type genotype. Therefore these allelic variants in the canine Cox-2 gene are associated with this disease in these breeds. . . . These alleles were shown to have 100% correlation with clinical cases of RD in 19 breeds. Finally, it is not easy to reconcile these results with the single causative mutation claimed on the DOGenes website. Consistent with the concerns just listed, the editors of the journal in which the paper by Whitely et al. (2011) was published have themselves published an Expression of Concern in order to make readers aware of the concerns about the reliability of the results and conclusions reported in the article (PLOS ONE Editors, 2012) The effects of the above alleles on methylation of the PTGS2 (COX-2) promoter in 13 dogs from 9 breeds were reported by Whiteley (2014). Eight of these dogs had biopsy (clinical) results: each of the five biopsy+ dogs come from a different breed, and two of the three biopsy- dogs have nothing but mutant alleles. Whiteley (2014) reported that The allelic variants were associated with hypermethylation of the Cox-2 promoter only in clinical cases of RD. The wild-type allele was never methylated, even in clinical cases that were heterozygous for a mutant allele. In cases that were biopsy-negative, the promoter remained unmethylated, regardless of the genotype. Homozygosity for a mutant allele or heterozygosity for two mutant alleles does not necessarily indicate that a dog is affected. Safra et al. (2015) reinforced the above doubts about the utility of the DNA test: they evaluated sequences [corresponding to those used in the DNA test] from dogs free of renal disease, and from gray wolves; the dog’s direct wild ancestor . . . . [Their] findings suggest that regional variants [the ones used in the DNA test] are a common finding in dogs and do not present a genetic risk for RD.`\n## Causal variant(s)\nDerived from OMIA database dump (omia.xml, local); structured field, not verbatim prose.\n- Variant: chromosome 12; nt change c.647-36_647-35insN[226]; pathogenicity class 1 — OMIA Variant / Variant_Phene\n\n## Evidence (references)\nDerived from OMIA database dump (omia.xml, local); structured field, not verbatim prose.\n- 1989. Renal Dysplasia in a Cavalier King Charles Spaniel. Irish Veterinary Journal — OMIA Phene_Article / Article\n- 1995. Renal dysplasia in Golden Retrievers. Veterinary Pathology — PubMed:PMID7604504 — OMIA Phene_Article / Article\n- 1996. Renal dysplasia in a Rhodesian Ridgeback dog. Journal of Small Animal Practice — PubMed:PMID8934429 — OMIA Phene_Article / Article\n- 1997. Calcinosis circumscripta and renal dysplasia in a dog.. Vet Dermatol — PubMed:PMID34645029 | DOI:10.1111/j.1365-3164.1997.tb00260.x — OMIA Phene_Article / Article\n- 1997. A control of a Golden Retriever with renal dysplasia. Journal of Veterinary Medical Science — PubMed:PMID9362046 — OMIA Phene_Article / Article\n- 1997. Ultrasonographic findings of renal dysplasia in Cocker Spaniels - eight cases. Acta Veterinaria Hungarica — PubMed:PMID9557317 — OMIA Phene_Article / Article\n- 1998. Renal dysplasia in three young adult Dutch kooiker dogs. Veterinary Quarterly — PubMed:PMID9810631 — OMIA Phene_Article / Article\n- 1999. Congenital renal dysplasia and psychogenic polydipsia in a Bernese mountain dog. Canadian Veterinary Journal - Revue Veterinaire Canadienne — OMIA Phene_Article / Article\n- 2000. Renal dysplasia in boxers and Finnish harriers. Journal of Small Animal Practice — PubMed:PMID11023130 — OMIA Phene_Article / Article\n- 2011. Novel allelic variants in the canine cyclooxgenase-2 (Cox-2) promoter are associated with renal dysplasia in dogs.. PLoS One — PubMed:PMID21346820 | DOI:10.1371/journal.pone.0016684 — OMIA Phene_Article / Article\n- 2010. Renal dysplasia in Beagle dogs: four cases.. Toxicol Pathol — PubMed:PMID20884818 | DOI:10.1177/0192623310382558 — OMIA Phene_Article / Article\n- 2010. Ultrasonographic findings in Cairn Terriers with preclinical renal dysplasia.. Vet Radiol Ultrasound — PubMed:PMID20806879 — OMIA Phene_Article / Article\n- (7 additional references in OMIA)\n\n## Comparative medicine (human OMIM)\nDerived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. Links this animal disorder to its human OMIM entry for comparative/translational context.\n- OMIM:248250 (type: trait) — OMIA Group_OMIM (via OMIA_ID)\n## Causal variant(s)\nDerived from OMIA database dump (omia.xml, local); structured field, not verbatim prose.\n- Variant: chromosome 12; nt change c.647-36_647-35insN[226]; pathogenicity class 1 — OMIA Variant / Variant_Phene\n\n## Evidence (references)\nDerived from OMIA database dump (omia.xml, local); structured field, not verbatim prose.\n- 1989. Renal Dysplasia in a Cavalier King Charles Spaniel. Irish Veterinary Journal — OMIA Phene_Article / Article\n- 1995. Renal dysplasia in Golden Retrievers. Veterinary Pathology — PubMed:PMID7604504 — OMIA Phene_Article / Article\n- 1996. Renal dysplasia in a Rhodesian Ridgeback dog. Journal of Small Animal Practice — PubMed:PMID8934429 — OMIA Phene_Article / Article\n- 1997. Calcinosis circumscripta and renal dysplasia in a dog. Vet Dermatol — PubMed:PMID34645029 | DOI:10.1111/j.1365-3164.1997.tb00260.x — OMIA Phene_Article / Article\n- 1997. A control of a Golden Retriever with renal dysplasia. Journal of Veterinary Medical Science — PubMed:PMID9362046 — OMIA Phene_Article / Article\n- 1997. Ultrasonographic findings of renal dysplasia in Cocker Spaniels - eight cases. Acta Veterinaria Hungarica — PubMed:PMID9557317 — OMIA Phene_Article / Article\n- 1998. Renal dysplasia in three young adult Dutch kooiker dogs. Veterinary Quarterly — PubMed:PMID9810631 — OMIA Phene_Article / Article\n- 1999. Congenital renal dysplasia and psychogenic polydipsia in a Bernese mountain dog. Canadian Veterinary Journal - Revue Veterinaire Canadienne — OMIA Phene_Article / Article\n- 2000. Renal dysplasia in boxers and Finnish harriers. Journal of Small Animal Practice — PubMed:PMID11023130 — OMIA Phene_Article / Article\n- 2011. Novel allelic variants in the canine cyclooxgenase-2 (Cox-2) promoter are associated with renal dysplasia in dogs. PLoS One — PubMed:PMID21346820 | DOI:10.1371/journal.pone.0016684 — OMIA Phene_Article / Article\n- 2010. Renal dysplasia in Beagle dogs: four cases. Toxicol Pathol — PubMed:PMID20884818 | DOI:10.1177/0192623310382558 — OMIA Phene_Article / Article\n- 2010. Ultrasonographic findings in Cairn Terriers with preclinical renal dysplasia. Vet Radiol Ultrasound — PubMed:PMID20806879 — OMIA Phene_Article / Article\n- (7 additional references in OMIA)\n\n## Comparative medicine (human OMIM)\nDerived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. Links this animal disorder to its human OMIM entry for comparative/translational context.\n- OMIM:248250 (type: trait) — OMIA Group_OMIM (via OMIA_ID)\n## Causal variant(s)\nDerived 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.\n- Variant: chromosome 12; nt change c.647-36_647-35insN[226]; pathogenicity class 1 — OMIA Variant / Variant_Phene\n\n## Evidence (references)\nDerived 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.\n- 1989. Renal Dysplasia in a Cavalier King Charles Spaniel. Irish Veterinary Journal — OMIA Phene_Article / Article\n- 1995. Renal dysplasia in Golden Retrievers. Veterinary Pathology — PubMed:PMID7604504 — OMIA Phene_Article / Article\n- 1996. Renal dysplasia in a Rhodesian Ridgeback dog. Journal of Small Animal Practice — PubMed:PMID8934429 — OMIA Phene_Article / Article\n- 1997. Calcinosis circumscripta and renal dysplasia in a dog. Vet Dermatol — PubMed:PMID34645029 | DOI:10.1111/j.1365-3164.1997.tb00260.x — OMIA Phene_Article / Article\n- 1997. A control of a Golden Retriever with renal dysplasia. Journal of Veterinary Medical Science — PubMed:PMID9362046 — OMIA Phene_Article / Article\n- 1997. Ultrasonographic findings of renal dysplasia in Cocker Spaniels - eight cases. Acta Veterinaria Hungarica — PubMed:PMID9557317 — OMIA Phene_Article / Article\n- 1998. Renal dysplasia in three young adult Dutch kooiker dogs. Veterinary Quarterly — PubMed:PMID9810631 — OMIA Phene_Article / Article\n- 1999. Congenital renal dysplasia and psychogenic polydipsia in a Bernese mountain dog. Canadian Veterinary Journal - Revue Veterinaire Canadienne — OMIA Phene_Article / Article\n- 2000. Renal dysplasia in boxers and Finnish harriers. Journal of Small Animal Practice — PubMed:PMID11023130 — OMIA Phene_Article / Article\n- 2011. Novel allelic variants in the canine cyclooxgenase-2 (Cox-2) promoter are associated with renal dysplasia in dogs. PLoS One — PubMed:PMID21346820 | DOI:10.1371/journal.pone.0016684 — OMIA Phene_Article / Article\n- 2010. Renal dysplasia in Beagle dogs: four cases. Toxicol Pathol — PubMed:PMID20884818 | DOI:10.1177/0192623310382558 — OMIA Phene_Article / Article\n- 2010. Ultrasonographic findings in Cairn Terriers with preclinical renal dysplasia. Vet Radiol Ultrasound — PubMed:PMID20806879 — OMIA Phene_Article / Article\n- (7 additional references in OMIA)\n\n## Comparative medicine (human OMIM)\nDerived 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.\n- OMIM:248250 (type: trait) — OMIA Group_OMIM (via OMIA_ID)\nverification_derived:\n  method: derived_from_dataset\n  source: \"OMIA database dump (omia.xml, local); fields Gene/Variant/Article/OMIM\"\n  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.\"\n## Causal variant(s)\nDerived 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.\n- Variant: chromosome 12; nt change c.647-36_647-35insN[226]; pathogenicity class 1 — OMIA Variant / Variant_Phene\n\n## Evidence (references)\nDerived 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.\n- 1989. Renal Dysplasia in a Cavalier King Charles Spaniel. Irish Veterinary Journal — OMIA Phene_Article / Article\n- 1995. Renal dysplasia in Golden Retrievers. Veterinary Pathology — PubMed:PMID7604504 — OMIA Phene_Article / Article\n- 1996. Renal dysplasia in a Rhodesian Ridgeback dog. Journal of Small Animal Practice — PubMed:PMID8934429 — OMIA Phene_Article / Article\n- 1997. Calcinosis circumscripta and renal dysplasia in a dog. Vet Dermatol — PubMed:PMID34645029 | DOI:10.1111/j.1365-3164.1997.tb00260.x — OMIA Phene_Article / Article\n- 1997. A control of a Golden Retriever with renal dysplasia. Journal of Veterinary Medical Science — PubMed:PMID9362046 — OMIA Phene_Article / Article\n- 1997. Ultrasonographic findings of renal dysplasia in Cocker Spaniels - eight cases. Acta Veterinaria Hungarica — PubMed:PMID9557317 — OMIA Phene_Article / Article\n- 1998. Renal dysplasia in three young adult Dutch kooiker dogs. Veterinary Quarterly — PubMed:PMID9810631 — OMIA Phene_Article / Article\n- 1999. Congenital renal dysplasia and psychogenic polydipsia in a Bernese mountain dog. Canadian Veterinary Journal - Revue Veterinaire Canadienne — OMIA Phene_Article / Article\n- 2000. Renal dysplasia in boxers and Finnish harriers. Journal of Small Animal Practice — PubMed:PMID11023130 — OMIA Phene_Article / Article\n- 2011. Novel allelic variants in the canine cyclooxgenase-2 (Cox-2) promoter are associated with renal dysplasia in dogs. PLoS One — PubMed:PMID21346820 | DOI:10.1371/journal.pone.0016684 — OMIA Phene_Article / Article\n- 2010. Renal dysplasia in Beagle dogs: four cases. Toxicol Pathol — PubMed:PMID20884818 | DOI:10.1177/0192623310382558 — OMIA Phene_Article / Article\n- 2010. Ultrasonographic findings in Cairn Terriers with preclinical renal dysplasia. Vet Radiol Ultrasound — PubMed:PMID20806879 — OMIA Phene_Article / Article\n- (7 additional references in OMIA)\n\n## Comparative medicine (human OMIM)\nDerived 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.\n- OMIM:248250 (type: trait) — OMIA Group_OMIM (via OMIA_ID)\nverification_derived:\n  method: derived_from_dataset\n  source: \"OMIA database dump (omia.xml, local); fields Gene/Variant/Article/OMIM\"\n  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.\"\n## Causal variant(s)\nDerived 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.\n- Variant: chromosome 12; nt change c.647-36_647-35insN[226]; pathogenicity class 1 — OMIA Variant / Variant_Phene\n\n## Evidence (references)\nDerived 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.\n- 1989. Renal Dysplasia in a Cavalier King Charles Spaniel. Irish Veterinary Journal — OMIA Phene_Article / Article\n- 1995. Renal dysplasia in Golden Retrievers. Veterinary Pathology — PubMed:PMID7604504 — OMIA Phene_Article / Article\n- 1996. Renal dysplasia in a Rhodesian Ridgeback dog. Journal of Small Animal Practice — PubMed:PMID8934429 — OMIA Phene_Article / Article\n- 1997. Calcinosis circumscripta and renal dysplasia in a dog. Vet Dermatol — PubMed:PMID34645029 | DOI:10.1111/j.1365-3164.1997.tb00260.x — OMIA Phene_Article / Article\n- 1997. A control of a Golden Retriever with renal dysplasia. Journal of Veterinary Medical Science — PubMed:PMID9362046 — OMIA Phene_Article / Article\n- 1997. Ultrasonographic findings of renal dysplasia in Cocker Spaniels - eight cases. Acta Veterinaria Hungarica — PubMed:PMID9557317 — OMIA Phene_Article / Article\n- 1998. Renal dysplasia in three young adult Dutch kooiker dogs. Veterinary Quarterly — PubMed:PMID9810631 — OMIA Phene_Article / Article\n- 1999. Congenital renal dysplasia and psychogenic polydipsia in a Bernese mountain dog. Canadian Veterinary Journal - Revue Veterinaire Canadienne — OMIA Phene_Article / Article\n- 2000. Renal dysplasia in boxers and Finnish harriers. Journal of Small Animal Practice — PubMed:PMID11023130 — OMIA Phene_Article / Article\n- 2011. Novel allelic variants in the canine cyclooxgenase-2 (Cox-2) promoter are associated with renal dysplasia in dogs. PLoS One — PubMed:PMID21346820 | DOI:10.1371/journal.pone.0016684 — OMIA Phene_Article / Article\n- 2010. Renal dysplasia in Beagle dogs: four cases. Toxicol Pathol — PubMed:PMID20884818 | DOI:10.1177/0192623310382558 — OMIA Phene_Article / Article\n- 2010. Ultrasonographic findings in Cairn Terriers with preclinical renal dysplasia. Vet Radiol Ultrasound — PubMed:PMID20806879 — OMIA Phene_Article / Article\n- (7 additional references in OMIA)\n\n## Comparative medicine (human OMIM)\nDerived 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.\n- OMIM:248250 (type: trait) — OMIA Group_OMIM (via OMIA_ID)\nverification_derived:\n  method: derived_from_dataset\n  source: \"OMIA database dump (omia.xml, local); fields Gene/Variant/Article/OMIM\"\n  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.\"\n","sources":["companion-breed-health — Cavalier King Charles Spaniel — Renal dysplasia (hereditary; OMIA-verified breed predisposition)"],"source":{"authority":"companion-breed-health","title":"Cavalier King Charles Spaniel — Renal dysplasia (hereditary; OMIA-verified breed predisposition)","url":"https://pubmed.ncbi.nlm.nih.gov/7604504/","retrieved":"","ref":"PMID 7604504","doc_type":"official source","source_document":"","verification_file":""},"source_document":"","source_file":"","trust":{"authority_tier":"ungraded","fidelity":"verbatim","license":null,"display_grade":"pending"},"tokens_estimated":3508,"generated_at":null,"tip":"Use /api/v1/topics to discover more topics. /api/v1/nutrient for precise single-point queries. /api/v1/cross_compare for 2-3 standard comparisons."}