SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC)
We investigated two litters of distantly related Nova Scotia Duck Tolling Retrievers (NSDTR), of which four puppies were affected by cerebellar signs with or without neuromuscular weakness. The phenotype was termed cerebellar degeneration—myositis complex (CDMC). We suspected a heritable condition a...
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ftdoajarticles:oai:doaj.org/article:e63d67b7b7c0456085dc5a239b62072f 2023-05-15T15:50:26+02:00 SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC) Matthias Christen Stefan Rupp Iris Van Soens Sofie F. M. Bhatti Kaspar Matiasek Thilo von Klopmann Vidhya Jagannathan Indiana Madden Kevin Batcher Danika Bannasch Tosso Leeb 2022-07-01T00:00:00Z https://doi.org/10.3390/genes13071223 https://doaj.org/article/e63d67b7b7c0456085dc5a239b62072f EN eng MDPI AG https://www.mdpi.com/2073-4425/13/7/1223 https://doaj.org/toc/2073-4425 doi:10.3390/genes13071223 2073-4425 https://doaj.org/article/e63d67b7b7c0456085dc5a239b62072f Genes, Vol 13, Iss 1223, p 1223 (2022) Canis lupus familiaris neurology seizure N-acetyl aspartic acid aralar precision medicine Genetics QH426-470 article 2022 ftdoajarticles https://doi.org/10.3390/genes13071223 2022-12-30T23:48:58Z We investigated two litters of distantly related Nova Scotia Duck Tolling Retrievers (NSDTR), of which four puppies were affected by cerebellar signs with or without neuromuscular weakness. The phenotype was termed cerebellar degeneration—myositis complex (CDMC). We suspected a heritable condition and initiated a genetic analysis. The genome of one affected dog was sequenced and compared to 565 control genomes. This search yielded a private protein-changing SLC25A12 variant in the affected dog, XM_038584842.1:c.1337C>T, predicted to result in the amino acid change XP_038440770.1:(p.Pro446Leu). The genotypes at the variant co-segregated with the phenotype as expected for a monogenic autosomal recessive mode of inheritance in both litters. Genotyping of 533 additional NSDTR revealed variant allele frequencies of 3.6% and 1.3% in a European and a North American cohort, respectively. The available clinical and biochemical data, together with current knowledge about SLC25A12 variants and their functional impact in humans, mice, and dogs, suggest the p.Pro446Leu variant is a candidate causative defect for the observed phenotype in the affected dogs. Article in Journal/Newspaper Canis lupus Directory of Open Access Journals: DOAJ Articles Genes 13 7 1223 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Canis lupus familiaris neurology seizure N-acetyl aspartic acid aralar precision medicine Genetics QH426-470 |
spellingShingle |
Canis lupus familiaris neurology seizure N-acetyl aspartic acid aralar precision medicine Genetics QH426-470 Matthias Christen Stefan Rupp Iris Van Soens Sofie F. M. Bhatti Kaspar Matiasek Thilo von Klopmann Vidhya Jagannathan Indiana Madden Kevin Batcher Danika Bannasch Tosso Leeb SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC) |
topic_facet |
Canis lupus familiaris neurology seizure N-acetyl aspartic acid aralar precision medicine Genetics QH426-470 |
description |
We investigated two litters of distantly related Nova Scotia Duck Tolling Retrievers (NSDTR), of which four puppies were affected by cerebellar signs with or without neuromuscular weakness. The phenotype was termed cerebellar degeneration—myositis complex (CDMC). We suspected a heritable condition and initiated a genetic analysis. The genome of one affected dog was sequenced and compared to 565 control genomes. This search yielded a private protein-changing SLC25A12 variant in the affected dog, XM_038584842.1:c.1337C>T, predicted to result in the amino acid change XP_038440770.1:(p.Pro446Leu). The genotypes at the variant co-segregated with the phenotype as expected for a monogenic autosomal recessive mode of inheritance in both litters. Genotyping of 533 additional NSDTR revealed variant allele frequencies of 3.6% and 1.3% in a European and a North American cohort, respectively. The available clinical and biochemical data, together with current knowledge about SLC25A12 variants and their functional impact in humans, mice, and dogs, suggest the p.Pro446Leu variant is a candidate causative defect for the observed phenotype in the affected dogs. |
format |
Article in Journal/Newspaper |
author |
Matthias Christen Stefan Rupp Iris Van Soens Sofie F. M. Bhatti Kaspar Matiasek Thilo von Klopmann Vidhya Jagannathan Indiana Madden Kevin Batcher Danika Bannasch Tosso Leeb |
author_facet |
Matthias Christen Stefan Rupp Iris Van Soens Sofie F. M. Bhatti Kaspar Matiasek Thilo von Klopmann Vidhya Jagannathan Indiana Madden Kevin Batcher Danika Bannasch Tosso Leeb |
author_sort |
Matthias Christen |
title |
SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC) |
title_short |
SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC) |
title_full |
SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC) |
title_fullStr |
SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC) |
title_full_unstemmed |
SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC) |
title_sort |
slc25a12 missense variant in nova scotia duck tolling retrievers affected by cerebellar degeneration—myositis complex (cdmc) |
publisher |
MDPI AG |
publishDate |
2022 |
url |
https://doi.org/10.3390/genes13071223 https://doaj.org/article/e63d67b7b7c0456085dc5a239b62072f |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes, Vol 13, Iss 1223, p 1223 (2022) |
op_relation |
https://www.mdpi.com/2073-4425/13/7/1223 https://doaj.org/toc/2073-4425 doi:10.3390/genes13071223 2073-4425 https://doaj.org/article/e63d67b7b7c0456085dc5a239b62072f |
op_doi |
https://doi.org/10.3390/genes13071223 |
container_title |
Genes |
container_volume |
13 |
container_issue |
7 |
container_start_page |
1223 |
_version_ |
1766385371838414848 |