OMIA:002244-9615 : Craniomandibular osteopathy, SLC37A2-related in Canis lupus familiaris
Categories: Craniofacial phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 619136 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant with incomplete penetrance
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2016
Cross-species summary: See also OMIA 000236 : Craniomandibular osteopathy, generic
Inheritance: Padgett and Mostosky (1965) concluded autosomal recessive inheritance in the West Highland White terrier breed.
Hytönen et al. (2016) reported that "The determination of the exact mode of inheritance in dogs [in West Highland White Terriers, Cairn Terriers and Scottish Terriers] is not straightforward due to the nature of the leaky splice variant and mild self-limiting phenotype that may remain unobserved and prevent retrospective diagnosis. We found some dogs that were homozygous for the variant but had no reported clinical signs. However, we observed a considerable level of the wild-type SLC37A2 transcript in homozygous dogs in the peripheral blood due to the splicing leakage, suggesting that the leaky expression is sufficient to avoid a clinical phenotype in some cases. We also found several heterozygous dogs that had developed CMO. We found that heterozygous dogs had lower levels of wild-type SLC37A2 transcript compared to the unaffected dogs with individual variation of expression between dogs. This result suggested a dominant disease with incomplete penetrance that could help to explain the reported differences in the severity and duration of CMO among the affected dogs, although alternative models of inheritance cannot be completely ruled out yet."
Molecular basis: Hytönen et al. (2016) reported that a likely causal variant in West Highland White Terriers, Cairn Terriers and Scottish Terriers is a splicing variant "c.1332C>T in exon 15 of SLC37A2 . . . The mutant T allele eliminates a potential binding site for the splicing factor ASF/SF-2".
Letko et al. (2020) discovered a likely causal variant for this disorder: "in a Basset Hound, a heterozygous most likely pathogenic splice site variant was found in SLC37A2 (c.1446+1G>A), predicted to lead to exon skipping as shown before in SLC37A2‐associated canine CMO of Terriers."
Breeds: Basset Hound, Cairn Terrier, Scottish Terrier, West Highland White Terrier.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|SLC37A2||solute carrier family 37 (glucose-6-phosphate transporter), member 2||Canis lupus familiaris||5||NC_051809.1 (9346109..9323545)||SLC37A2||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|
|1158||Basset Hound||Craniomandibular osteopathy||SLC37A2||splicing||Naturally occurring variant||CanFam3.1||5||g.9387071C>T||c.1446+1G>A||NC_006587.3:g.9387071C>T; XM_005619600.3:c.1446+1G>A (Letko et al., 2020)||2020||32033218|
|411||Cairn Terrier Scottish Terrier West Highland White Terrier||Craniomandibular osteopathy||SLC37A2||splicing||Naturally occurring variant||CanFam3.1||5||g.9387327G>A||c.1332C>T||XM_005619600.3:c.1332C>T (Letko et al., 2020)||2016||27187611||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
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.
|2020||Letko, A., Leuthard, F., Jagannathan, V., Corlazzoli, D., Matiasek, K., Schweizer, D., Hytönen, M.K., Lohi, H., Leeb, T., Drögemüller, C. :|
|Whole genome sequencing indicates heterogeneity of hyperostotic disorders in dogs. Genes (Basel) 11:163, 2020. Pubmed reference: 32033218 . DOI: 10.3390/genes11020163.|
|2016||Hytönen, M.K., Arumilli, M., Lappalainen, A.K., Owczarek-Lipska, M., Jagannathan, V., Hundi, S., Salmela, E., Venta, P., Sarkiala, E., Jokinen, T., Gorgas, D., Kere, J., Nieminen, P., Drögemüller, C., Lohi, H. :|
|Molecular characterization of three canine models of human rare bone diseases: Caffey, van den Ende-Gupta, and Raine syndromes. PLoS Genet 12:e1006037, 2016. Pubmed reference: 27187611 . DOI: 10.1371/journal.pgen.1006037.|
|Hytönen, M.K., Lohi, H. :|
|Canine models of human rare disorders. Rare Dis 4:e1241362, 2016. Pubmed reference: 27803843 . DOI: 10.1080/21675511.2016.1241362.|
|2012||Pettitt, R., Fox, R., Comerford, E.J., Newitt, A. :|
|Bilateral angular carpal deformity in a dog with craniomandibular osteopathy. Vet Comp Orthop Traumatol 25:149-54, 2012. Pubmed reference: 22366888 . DOI: 10.3415/VCOT-11-02-0022.|
|2002||LaFond, E., Breur, G.J., Austin, C.C. :|
|Breed susceptibility for developmental orthopedic diseases in dogs Journal of the American Animal Hospital Association 38:467-477, 2002. Pubmed reference: 12220032 .|
|1994||Hudson, J.A., Montgomery, R.D., Hathcock, J.T., Jarboe, J.M. :|
|Computed tomography of craniomandibular osteopathy in a dog. Veterinary Radiology & Ultrasound 35:94-99, 1994.|
|1986||Gutteling, J., Hazewinkel, H.A. :|
|[Hyperostosis of the mandibles in a West Highland white terrier]. Tijdschr Diergeneeskd 111:1246-8, 1986. Pubmed reference: 3824324 .|
|Padgett, G.A., Mostosky, U.V. :|
|The mode of inheritance of craniomandibular osteopathy in West Highland White terrier dogs. Am J Med Genet 25:9-13, 1986. Pubmed reference: 3799725 . DOI: 10.1002/ajmg.1320250103.|
|1979||Thornburg, L.P. :|
|Infantile cortical hyperostosis (Caffey-Silverman syndrome). Animal model: craniomandibular osteopathy in the canine. Am J Pathol 95:575-8, 1979. Pubmed reference: 377993 .|
|1958||Littlewort, M.C.G. :|
|Tumor-like exostoses on the bones of the head in puppies. Veterinary Record 70:977-978, 1958.|
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