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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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Autores principales: Christen, Matthias, Rupp, Stefan, Van Soens, Iris, Bhatti, Sofie F. M., Matiasek, Kaspar, von Klopmann, Thilo, Jagannathan, Vidhya, Madden, Indiana, Batcher, Kevin, Bannasch, Danika, Leeb, Tosso
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319113/
https://www.ncbi.nlm.nih.gov/pubmed/35886006
http://dx.doi.org/10.3390/genes13071223
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author Christen, Matthias
Rupp, Stefan
Van Soens, Iris
Bhatti, Sofie F. M.
Matiasek, Kaspar
von Klopmann, Thilo
Jagannathan, Vidhya
Madden, Indiana
Batcher, Kevin
Bannasch, Danika
Leeb, Tosso
author_facet Christen, Matthias
Rupp, Stefan
Van Soens, Iris
Bhatti, Sofie F. M.
Matiasek, Kaspar
von Klopmann, Thilo
Jagannathan, Vidhya
Madden, Indiana
Batcher, Kevin
Bannasch, Danika
Leeb, Tosso
author_sort Christen, Matthias
collection PubMed
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.
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spelling pubmed-93191132022-07-27 SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC) Christen, Matthias Rupp, Stefan Van Soens, Iris Bhatti, Sofie F. M. Matiasek, Kaspar von Klopmann, Thilo Jagannathan, Vidhya Madden, Indiana Batcher, Kevin Bannasch, Danika Leeb, Tosso Genes (Basel) Article 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. MDPI 2022-07-09 /pmc/articles/PMC9319113/ /pubmed/35886006 http://dx.doi.org/10.3390/genes13071223 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Christen, Matthias
Rupp, Stefan
Van Soens, Iris
Bhatti, Sofie F. M.
Matiasek, Kaspar
von Klopmann, Thilo
Jagannathan, Vidhya
Madden, Indiana
Batcher, Kevin
Bannasch, Danika
Leeb, Tosso
SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC)
title 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_short 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)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319113/
https://www.ncbi.nlm.nih.gov/pubmed/35886006
http://dx.doi.org/10.3390/genes13071223
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