OMIA 002244-9615 : Craniomandibular osteopathy, SLC37A2-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 114000

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.

Associated gene:

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_006587.3 (9407631..9384368) SLC37A2 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Basset Hound Craniomandibular osteopathy SLC37A2 splicing CanFam3.1 5 g.9,387,071C>T c.1,446+1G>A NC_006587.3:g.9387071C>T; XM_005619600.3:c.1446+1G>A (Letko et al., 2020) 2020 32033218
Cairn Terrier Scottish Terrier West Highland White terrier Craniomandibular osteopathy SLC37A2 splicing CanFam3.1 5 g.9,387,327 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

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.
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:, 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.

Edit History


  • Created by Frank Nicholas on 12 Feb 2020
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