MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA)
We investigated a hereditary syndrome in Cane Corso dogs. 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. Combined linkage and ho...
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ftdoajarticles:oai:doaj.org/article:ef57614f30e14d95ae7bc6472b43482c 2023-05-15T15:50:37+02:00 MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) Matthias Christen Henriëtte Booij-Vrieling Jelena Oksa-Minalto Cynthia de Vries Alexandra Kehl Vidhya Jagannathan Tosso Leeb 2021-09-01T00:00:00Z https://doi.org/10.3390/genes12101497 https://doaj.org/article/ef57614f30e14d95ae7bc6472b43482c EN eng MDPI AG https://www.mdpi.com/2073-4425/12/10/1497 https://doaj.org/toc/2073-4425 doi:10.3390/genes12101497 2073-4425 https://doaj.org/article/ef57614f30e14d95ae7bc6472b43482c Genes, Vol 12, Iss 1497, p 1497 (2021) Canis lupus familiaris animal model endoplasmic reticulum TANGO1 collagen precision medicine Genetics QH426-470 article 2021 ftdoajarticles https://doi.org/10.3390/genes12101497 2022-12-31T07:30:01Z We investigated a hereditary syndrome in Cane Corso dogs. 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. Combined linkage and homozygosity mapping delineated a 5.8 Mb critical interval. 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. MIA3 variants had previously been shown to cause related phenotypes in humans and mice. Our data in dogs together with the existing functional knowledge of MIA3 variants in other mammalian species suggest the MIA3 splice defect and a near complete loss of gene function as causative molecular pathomechanism for the DSRA phenotype in the investigated dogs. Article in Journal/Newspaper Canis lupus Directory of Open Access Journals: DOAJ Articles Genes 12 10 1497 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Canis lupus familiaris animal model endoplasmic reticulum TANGO1 collagen precision medicine Genetics QH426-470 |
spellingShingle |
Canis lupus familiaris animal model endoplasmic reticulum TANGO1 collagen precision medicine Genetics QH426-470 Matthias Christen Henriëtte Booij-Vrieling Jelena Oksa-Minalto Cynthia de Vries Alexandra Kehl Vidhya Jagannathan Tosso Leeb MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
topic_facet |
Canis lupus familiaris animal model endoplasmic reticulum TANGO1 collagen precision medicine Genetics QH426-470 |
description |
We investigated a hereditary syndrome in Cane Corso dogs. 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. Combined linkage and homozygosity mapping delineated a 5.8 Mb critical interval. 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. MIA3 variants had previously been shown to cause related phenotypes in humans and mice. Our data in dogs together with the existing functional knowledge of MIA3 variants in other mammalian species suggest the MIA3 splice defect and a near complete loss of gene function as causative molecular pathomechanism for the DSRA phenotype in the investigated dogs. |
format |
Article in Journal/Newspaper |
author |
Matthias Christen Henriëtte Booij-Vrieling Jelena Oksa-Minalto Cynthia de Vries Alexandra Kehl Vidhya Jagannathan Tosso Leeb |
author_facet |
Matthias Christen Henriëtte Booij-Vrieling Jelena Oksa-Minalto Cynthia de Vries Alexandra Kehl Vidhya Jagannathan Tosso Leeb |
author_sort |
Matthias Christen |
title |
MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
title_short |
MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
title_full |
MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
title_fullStr |
MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
title_full_unstemmed |
MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
title_sort |
mia3 splice defect in cane corso dogs with dental-skeletal-retinal anomaly (dsra) |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doi.org/10.3390/genes12101497 https://doaj.org/article/ef57614f30e14d95ae7bc6472b43482c |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes, Vol 12, Iss 1497, p 1497 (2021) |
op_relation |
https://www.mdpi.com/2073-4425/12/10/1497 https://doaj.org/toc/2073-4425 doi:10.3390/genes12101497 2073-4425 https://doaj.org/article/ef57614f30e14d95ae7bc6472b43482c |
op_doi |
https://doi.org/10.3390/genes12101497 |
container_title |
Genes |
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12 |
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10 |
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1497 |
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1766385613342244864 |