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A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration
BACKGROUND: A variety of presumed hereditary, neurologic diseases have been reported in young Rottweilers. Overlapping ages of onset and clinical signs have made antemortem diagnosis difficult. One of these diseases, neuronal vacuolation and spinocerebellar degeneration (NVSD) shares clinical and hi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913561/ https://www.ncbi.nlm.nih.gov/pubmed/26968732 http://dx.doi.org/10.1111/jvim.13921 |
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author | Mhlanga‐Mutangadura, T. Johnson, G.S. Ashwini, A. Shelton, G.D. Wennogle, S.A. Johnson, G.C. Kuroki, K. O'Brien, D.P. |
author_facet | Mhlanga‐Mutangadura, T. Johnson, G.S. Ashwini, A. Shelton, G.D. Wennogle, S.A. Johnson, G.C. Kuroki, K. O'Brien, D.P. |
author_sort | Mhlanga‐Mutangadura, T. |
collection | PubMed |
description | BACKGROUND: A variety of presumed hereditary, neurologic diseases have been reported in young Rottweilers. Overlapping ages of onset and clinical signs have made antemortem diagnosis difficult. One of these diseases, neuronal vacuolation and spinocerebellar degeneration (NVSD) shares clinical and histological features with polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV), a recently described hereditary disease in Black Russian Terriers (BRTs). Dogs with POANV harbor mutations in RAB3GAP1 which codes for a protein involved in membrane trafficking. HYPOTHESIS: Rottweilers with NVSD will be homozygous for the RAB3GAP1:c.743delC allele associated with POANV in BRTs. ANIMALS: Eight Rottweilers with NVSD confirmed at necropsy, 128 Rottweilers without early onset neurologic signs, and 468 randomly selected dogs from 169 other breeds. METHODS: Retrospective case–control study. Dogs were genotyped for the RAB3GAP1:c.743delC allele with an allelic discrimination assay. RESULTS: All 8 NVSD‐affected dogs were homozygous for the RAB3GAP1:c.743delC allele while the 128 NVSD‐free Rottweilers were either homozygous for the reference allele (n = 105) or heterozygous (n = 23) and the 468 genotyped dogs from other breeds were all homozygous for the reference allele. CONCLUSIONS AND CLINICAL IMPORTANCE: The RAB3GAP1:c.743delC mutation is associated with a similar phenotype in Rottweilers and BRTs. Identification of the mutation permits a DNA test that can aid in the diagnosis of NVSD and identify carriers of the trait so that breeders can avoid producing affected dogs. Disruption of membrane trafficking could explain the neuronal vacuolation seen in NVSD and other spongiform encephalopathies. |
format | Online Article Text |
id | pubmed-4913561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-49135612016-06-22 A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration Mhlanga‐Mutangadura, T. Johnson, G.S. Ashwini, A. Shelton, G.D. Wennogle, S.A. Johnson, G.C. Kuroki, K. O'Brien, D.P. J Vet Intern Med SMALL ANIMAL BACKGROUND: A variety of presumed hereditary, neurologic diseases have been reported in young Rottweilers. Overlapping ages of onset and clinical signs have made antemortem diagnosis difficult. One of these diseases, neuronal vacuolation and spinocerebellar degeneration (NVSD) shares clinical and histological features with polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV), a recently described hereditary disease in Black Russian Terriers (BRTs). Dogs with POANV harbor mutations in RAB3GAP1 which codes for a protein involved in membrane trafficking. HYPOTHESIS: Rottweilers with NVSD will be homozygous for the RAB3GAP1:c.743delC allele associated with POANV in BRTs. ANIMALS: Eight Rottweilers with NVSD confirmed at necropsy, 128 Rottweilers without early onset neurologic signs, and 468 randomly selected dogs from 169 other breeds. METHODS: Retrospective case–control study. Dogs were genotyped for the RAB3GAP1:c.743delC allele with an allelic discrimination assay. RESULTS: All 8 NVSD‐affected dogs were homozygous for the RAB3GAP1:c.743delC allele while the 128 NVSD‐free Rottweilers were either homozygous for the reference allele (n = 105) or heterozygous (n = 23) and the 468 genotyped dogs from other breeds were all homozygous for the reference allele. CONCLUSIONS AND CLINICAL IMPORTANCE: The RAB3GAP1:c.743delC mutation is associated with a similar phenotype in Rottweilers and BRTs. Identification of the mutation permits a DNA test that can aid in the diagnosis of NVSD and identify carriers of the trait so that breeders can avoid producing affected dogs. Disruption of membrane trafficking could explain the neuronal vacuolation seen in NVSD and other spongiform encephalopathies. John Wiley and Sons Inc. 2016-03-10 2016 /pmc/articles/PMC4913561/ /pubmed/26968732 http://dx.doi.org/10.1111/jvim.13921 Text en Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | SMALL ANIMAL Mhlanga‐Mutangadura, T. Johnson, G.S. Ashwini, A. Shelton, G.D. Wennogle, S.A. Johnson, G.C. Kuroki, K. O'Brien, D.P. A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration |
title | A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration |
title_full | A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration |
title_fullStr | A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration |
title_full_unstemmed | A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration |
title_short | A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration |
title_sort | homozygous rab3gap1:c.743delc mutation in rottweilers with neuronal vacuolation and spinocerebellar degeneration |
topic | SMALL ANIMAL |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913561/ https://www.ncbi.nlm.nih.gov/pubmed/26968732 http://dx.doi.org/10.1111/jvim.13921 |
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