OMIA 002465-9615 : Dental-skeletal-retinal anomaly, MIA3-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 613455 (gene) , 619269 (trait)

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.

Associated gene:

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

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.

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

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.
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.

Edit History


  • Created by Imke Tammen2 on 29 Oct 2021
  • Changed by Tosso Leeb on 29 Oct 2021