Categories: Skeleton phene (incl. short stature & teeth)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 613455 (gene) , 619269 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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 (Dog) (VBO_0200712).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: