OMIA:001886-9615 : Chondrodysplasia, disproportionate short-limbed in Canis lupus familiaris
Categories: Skeleton phene (incl. short stature & teeth)
Possibly relevant human trait(s) and/or gene(s) (MIM number): 604042 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2013
History: This specific type of chondrodysplasia was first reported by Bingel and Sande (1982) in Norwegian Elkhounds.
Inheritance: Kyöstilä et al. (2013) provided strong evidence of autosomal recessive inheritance.
Mapping: By conducting a GWAS on nine affected and nine control Norwegian Elkhounds, each genotyped with the Illumina CanineSNP20 SNP Chip (yielding 14,626 informative SNPs), Kyöstilä et al. (2013) mapped the disorder to a 2Mb region (from 60 to 62 Mb (CanFam2.0 assembly)) of chromosome CFA17, containing 33 genes.
Molecular basis: The most likely functional candidate gene in the region mapped by Kyöstilä et al. (2013) (see above) was ITAG10, encoding integrin subunit alpha 10. Sequencing all exons in this gene in two affecteds, an obligate carrier and a half-sib of an affected dog, revealed four exonic SNVs, namely three synonymous and one nonsense (c.2083C>T in exon 16; p.Arg695*). Widespread genotyping of the latter in families of Norwegian Elkhounds and Karelian bear dog, each segregating this disorder, indicated it to be the causal mutation.
Clinical features: As reported by Bingel and Sande (1982): "Radiographic changes included flaring and increased width of the distal metaphyses of the radius and ulna, delayed ossification of the cuboid bones of the carpus, and reduction in length of the vertebral bodies. The zone of chondrocyte proliferation was decreased in width and contained areas of abnormal cell column formation alternated with wide areas of matrix. Chondrocytes in all zones contained one or more inclusions bounded by a smooth discontinuous membrane. The material within the inclusions appeared homogeneous and stained blue-green with Movat's pentachrome and deep blue with alcian blue-periodic acid-Schiff at pH 1.0 and 2.6. The distribution of ruthenium red granules in the matrix frequently revealed poor differentiation into territorial and interterritorial zones".
Prevalence: As reported by Kyöstilä et al. (2013), "Carrier frequency of the c.2083C>T mutation was 24% in a cohort of 156 randomly selected Finnish NEs [Norwegian Elkhound] and 8% in a population sample of 287 KBDs [Karelian bear dog]".
Breeds: Karelian bear dog, Norwegian Elkhound.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ITGA10||integrin, alpha 10||Canis lupus familiaris||17||NC_051821.1 (59709253..59692674)||ITGA10||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|
|336||Karelian bear dog Norwegian Elkhound||Chondrodysplasia, disproportionate short-limbed||ITGA10||nonsense (stop-gain)||Naturally occurring variant||CanFam3.1||17||g.58703935G>A||c.2083C>T||p.(R695*)||XM_845262.4; XP_850355.1||2013||24086591||Genomic coordinates in CanFam3.1 provided by Robert Kuhn|
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.
|2013||Kyöstilä, K., Lappalainen, A.K., Lohi, H. :|
|Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. PLoS One 8:e75621, 2013. Pubmed reference: 24086591 . DOI: 10.1371/journal.pone.0075621.|
|1982||Bingel, S.A., Sande, R.D. :|
|Chondrodysplasia in the Norwegian Elkhound American Journal of Pathology 107:219-, 1982. Pubmed reference: 7081383 .|
- Created by Frank Nicholas on 13 Oct 2013
- Changed by Frank Nicholas on 13 Oct 2013