OMIA:002465-9615 : Dental-skeletal-retinal anomaly, MIA3-related in Canis lupus familiaris
Categories: Skeleton phene (incl. short stature & teeth)
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 613455 (gene) , 619269 (trait)
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: 2021
Species-specific symbol: DSRA
Mapping: Christen et al. (2021): "Combined linkage and homozygosity mapping delineated a 5.8 Mb critical interval."
Molecular basis: Christen et al. (2021) "The comparison of whole genome sequence data of an affected dog to 789 control genomes revealed a private homozygous splice region variant in the critical interval. It affected the MIA3 gene encoding the MIA SH3 domain ER export factor 3, which has an essential role in the export of collagen and other secreted proteins. The identified variant, XM_005640835.3:c.3822+3_3822+4del, leads to skipping of two exons from the wild type transcript, XM_005640835.3:r.3712_3822del. Genotypes at the variant were consistent with monogenic autosomal recessive mode of inheritance in a complete family and showed perfect genotype-phenotype association in 18 affected and 22 unaffected Cane Corso dogs."
The MIA3 gene encodes a transmembrane protein termed MIA SH3 domain ER export factor 3, which is also known under the alias name “transport and Golgi organization 1” (TANGO1) (Saito et al. 2009). MIA3 plays an important role in the transport of secretory cargo including collagens from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (Malhotra and Erlmann, 2015). The DSRA phenotype is probably largely due to defects in the correct synthesis and deposition of various types of collagens (Christen et al. 2021).
Clinical features: Christen et al. (2021): "Affected dogs developed dental-skeletal-retinal anomaly (DSRA), clinically characterized by brittle, discolored, translucent teeth, disproportionate growth and progressive retinal degeneration resulting in vision loss."
Breed: Italian Cane Corso.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MIA3||melanoma inhibitory activity family, member 3||Canis lupus familiaris||38||NC_006620.2 (19882015..19935940)||MIA3||Homologene, Ensembl , NCBI gene|
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
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|
|1374||Italian Cane Corso||Dental-skeletal-retinal anomaly||MIA3||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||38||g.16920529_16920530del||c.3822+3_3822+4del||p.(V1238_K1274del)||XM_005640835.3; XP_005640892.1; published as g.16920529_16920530delAT, leads to skipping of two exons: XM_005640835.3:r.3712_3822del||2021||34680893|
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.
|2021||Christen, M., Booij-Vrieling, H., Oksa-Minalto, J., de Vries, C., Kehl, A., Jagannathan, V., Leeb, T. :|
|<i>MIA3</i> Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA). Genes (Basel) 12:1497, 2021. Pubmed reference: 34680893 . DOI: 10.3390/genes12101497.|
|2015||Malhotra, V., Erlmann, P. :|
|The pathway of collagen secretion. Annu Rev Cell Dev Biol 31:109-24, 2015. Pubmed reference: 26422332 . DOI: 10.1146/annurev-cellbio-100913-013002.|
|2009||Saito, K., Chen, M., Bard, F., Chen, S., Zhou, H., Woodley, D., Polischuk, R., Schekman, R., Malhotra, V. :|
|TANGO1 facilitates cargo loading at endoplasmic reticulum exit sites. Cell 136:891-902, 2009. Pubmed reference: 19269366 . DOI: 10.1016/j.cell.2008.12.025.|
- Created by Imke Tammen2 on 29 Oct 2021
- Changed by Tosso Leeb on 29 Oct 2021